rs5031002

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000044.6(AR):c.2450-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,198,668 control chromosomes in the GnomAD database, including 229 homozygotes. There are 8,357 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 12 hom., 426 hem., cov: 22)

Exomes 𝑓: 0.023 ( 217 hom. 7931 hem. )

Consequence

AR
NM_000044.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.184

Publications

23 publications found

Variant links:

Genes affected

AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

AR Gene-Disease associations (from GenCC):

androgen insensitivity syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
Kennedy disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
partial androgen insensitivity syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
complete androgen insensitivity syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

AR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-67722783-G-A is Benign according to our data. Variant chrX-67722783-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0145 (1612/111198) while in subpopulation NFE AF = 0.0247 (1307/52985). AF 95% confidence interval is 0.0236. There are 12 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.2450-44G>A		intron_variant	Intron 6 of 7	ENST00000374690.9	NP_000035.2
AR	NM_001011645.3 link	c.854-44G>A		intron_variant	Intron 7 of 8		NP_001011645.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AR	ENST00000374690.9 link	c.2450-44G>A	intron_variant	Intron 6 of 7	1	NM_000044.6	ENSP00000363822.3	P10275-1
AR	ENST00000396044.8 link	c.2174-903G>A	intron_variant	Intron 4 of 4	1		ENSP00000379359.3	F5GZG9
AR	ENST00000396043.4 link	n.*798-44G>A	intron_variant	Intron 7 of 8	1		ENSP00000379358.4	A0A7I2PS51
AR	ENST00000612452.5 link	n.2450-44G>A	intron_variant	Intron 6 of 8	5		ENSP00000484033.2	P10275-1A0A087X1B6

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

1613

AN:

111144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.00291

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00342

Gnomad EAS

AF:

0.000285

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.00736

GnomAD2 exomes

AF:

0.0146

AC:

2561

AN:

175518

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.00322

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.00230

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0230

AC:

24994

AN:

1087470

Hom.:

217

Cov.:

AF XY:

0.0224

AC XY:

7931

AN XY:

354226

show subpopulations

African (AFR)

AF:

0.00317

AC:

AN:

26165

American (AMR)

AF:

0.00450

AC:

158

AN:

35084

Ashkenazi Jewish (ASJ)

AF:

0.00285

AC:

AN:

19292

East Asian (EAS)

AF:

0.0000668

AC:

AN:

29960

South Asian (SAS)

AF:

0.00850

AC:

455

AN:

53536

European-Finnish (FIN)

AF:

0.0198

AC:

800

AN:

40378

Middle Eastern (MID)

AF:

0.00707

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.0271

AC:

22590

AN:

833219

Other (OTH)

AF:

0.0180

AC:

822

AN:

45734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

910

1820

2729

3639

4549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

846

1692

2538

3384

4230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0145

AC:

1612

AN:

111198

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

426

AN XY:

33434

show subpopulations

African (AFR)

AF:

0.00357

AC:

109

AN:

30573

American (AMR)

AF:

0.00609

AC:

AN:

10514

Ashkenazi Jewish (ASJ)

AF:

0.00342

AC:

AN:

2628

East Asian (EAS)

AF:

0.000286

AC:

AN:

3495

South Asian (SAS)

AF:

0.00460

AC:

AN:

2611

European-Finnish (FIN)

AF:

0.0162

AC:

AN:

5978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0247

AC:

1307

AN:

52985

Other (OTH)

AF:

0.00728

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0215

Hom.:

1855

Bravo

AF:

0.0131

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 20150575) -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Oct 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

(source)

DANN

Benign

0.64

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over