rs2361634

Positions:

• chrX-67643001-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000374690.9(AR):​c.1617-255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 111,642 control chromosomes in the GnomAD database, including 125 homozygotes. There are 1,311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (125 hom., 1311 hem., cov: 23)
• Consequence: AR ENST00000374690.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-67643001-A-G is Benign according to our data. Variant chrX-67643001-A-G is described in ClinVar as [Benign]. Clinvar id is 1279480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6	c.1617-255A>G		intron_variant		ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.1617-255A>G		intron_variant		1	NM_000044.6	ENSP00000363822	P1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 4778 AN: 111588 Hom.: 126 Cov.: 23 AF XY: 0.0387 AC XY: 1308 AN XY: 33790

Gnomad AFR AF: 0.00921

Gnomad AMI AF: 0.0886

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.0238

Gnomad EAS AF: 0.000283

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0336

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0427 AC: 4772 AN: 111642 Hom.: 125 Cov.: 23 AF XY: 0.0387 AC XY: 1311 AN XY: 33854

Gnomad4 AFR AF: 0.00919

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0238

Gnomad4 EAS AF: 0.000284

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0205

Alfa AF: 0.0637 Hom.: 519

Bravo AF: 0.0384

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs2361634; hg19: chrX-66862843;