rs5918757

Variant names:

• chrX-67586188-G-A
• rs5918757
• NM_000044.6:c.1616+39426G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-67586188-G-A
• chrX-67586188-G-C
• chrX-67586188-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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
• Publications: 10 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6	c.1616+39426G>A		intron_variant	Intron 1 of 7	ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.1616+39426G>A		intron_variant	Intron 1 of 7	1	NM_000044.6	ENSP00000363822.3

Frequencies

GnomAD3 genomes AF: 0.732 AC: 80941 AN: 110562 Hom.: 22051 Cov.: 23

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

African (AFR) AF: 0.406 AC: 12358 AN: 30422

American (AMR) AF: 0.858 AC: 8927 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 2343 AN: 2644

East Asian (EAS) AF: 0.998 AC: 3467 AN: 3473

South Asian (SAS) AF: 0.915 AC: 2364 AN: 2583

European-Finnish (FIN) AF: 0.883 AC: 5172 AN: 5860

Middle Eastern (MID) AF: 0.809 AC: 174 AN: 215

European-Non Finnish (NFE) AF: 0.841 AC: 44406 AN: 52832

Other (OTH) AF: 0.767 AC: 1153 AN: 1503

Alfa AF: 0.808 Hom.: 28656

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
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5918757; hg19: chrX-66806030;