rs5918757

chrX-67586188-G-AchrX-67586188-G-CchrX-67586188-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000044.6(AR):c.1616+39426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (22041 hom., 24560 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High Homozygotes in GnomAd at 22051 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6	c.1616+39426G>A		intron_variant		ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9	c.1616+39426G>A		intron_variant		1	NM_000044.6	P1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 80941 AN: 110562 Hom.: 22051 Cov.: 23 AF XY: 0.748 AC XY: 24530 AN XY: 32814

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.764

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.732 AC: 80956 AN: 110611 Hom.: 22041 Cov.: 23 AF XY: 0.747 AC XY: 24560 AN XY: 32873

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.767

Alfa AF: 0.788 Hom.: 17317

Bravo AF: 0.722

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.3
Dann	Benign	0.57

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: rs5918757; hg19: chrX-66806030;