dbSNP rs150226204: AR:p.Arg212Arg (chrX-67545782-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000044.6(AR):c.636G>A(p.Arg212Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,210,606 control chromosomes in the GnomAD database, including 10 homozygotes. There are 1,498 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., 73 hem., cov: 22)

Exomes 𝑓: 0.0033 ( 9 hom. 1425 hem. )

Consequence

AR
NM_000044.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.672

Publications

1 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, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae)
Kennedy disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
partial androgen insensitivity syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-67545782-G-A is Benign according to our data. Variant chrX-67545782-G-A is described in ClinVar as Benign. ClinVar VariationId is 533381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.672 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00206 (232/112669) while in subpopulation SAS AF = 0.0171 (46/2690). AF 95% confidence interval is 0.0132. There are 1 homozygotes in GnomAd4. There are 73 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 73 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000044.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	NM_000044.6	MANE Select	c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 8	NP_000035.2
AR	NM_001348063.1		c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 4	NP_001334992.1	Q9NUA2
AR	NM_001348061.1		c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 4	NP_001334990.1	Q9NUA2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	ENST00000374690.9	TSL:1 MANE Select	c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 8	ENSP00000363822.3	P10275-1
AR	ENST00000396044.8	TSL:1	c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 5	ENSP00000379359.3	F5GZG9
AR	ENST00000504326.5	TSL:1	c.636G>A	p.Arg212Arg	synonymous	Exon 1 of 4	ENSP00000421155.1	P10275-3

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

232

AN:

112613

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000548

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00233

Gnomad ASJ

AF:

0.00263

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0171

Gnomad FIN

AF:

0.000160

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00242

Gnomad OTH

AF:

0.00330

GnomAD2 exomes

AF:

0.00367

AC:

667

AN:

181906

AF XY:

0.00464

show subpopulations

Gnomad AFR exome

AF:

0.000927

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000725

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00329

AC:

3617

AN:

1097937

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

1425

AN XY:

363311

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

26389

American (AMR)

AF:

0.00239

AC:

AN:

35187

Ashkenazi Jewish (ASJ)

AF:

0.00387

AC:

AN:

19380

East Asian (EAS)

AF:

0.0000994

AC:

AN:

30194

South Asian (SAS)

AF:

0.0179

AC:

969

AN:

54085

European-Finnish (FIN)

AF:

0.000148

AC:

AN:

40503

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00266

AC:

2243

AN:

841976

Other (OTH)

AF:

0.00371

AC:

171

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.00206

AC:

232

AN:

112669

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

34835

show subpopulations

African (AFR)

AF:

0.000547

AC:

AN:

31064

American (AMR)

AF:

0.00232

AC:

AN:

10761

Ashkenazi Jewish (ASJ)

AF:

0.00263

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3533

South Asian (SAS)

AF:

0.0171

AC:

AN:

2690

European-Finnish (FIN)

AF:

0.000160

AC:

AN:

6250

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00242

AC:

129

AN:

53277

Other (OTH)

AF:

0.00326

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00261

Hom.:

Bravo

AF:

0.00184

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Androgen resistance syndrome;C1839259:Kennedy disease (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.0

(source)

DANN

Benign

0.87

PhyloP100

0.67

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over