rs1361038

Variant names:

• chrX-67709844-G-A
• rs1361038
• NM_000044.6:c.1886-1558G>A

Variant summary

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

The NM_000044.6(AR):​c.1886-1558G>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 0.95 (35204 hom., 31479 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 3 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=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6	c.1886-1558G>A		intron_variant	Intron 3 of 7	ENST00000374690.9	NP_000035.2
AR	NM_001011645.3	c.290-1558G>A		intron_variant	Intron 4 of 8		NP_001011645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9	c.1886-1558G>A		intron_variant	Intron 3 of 7	1	NM_000044.6	ENSP00000363822.3
AR	ENST00000396044.8	c.1886-1558G>A		intron_variant	Intron 3 of 4	1		ENSP00000379359.3
AR	ENST00000396043.4	n.*234-1558G>A		intron_variant	Intron 4 of 8	1		ENSP00000379358.4
AR	ENST00000612452.5	n.1886-1558G>A		intron_variant	Intron 3 of 8	5		ENSP00000484033.2

Frequencies

GnomAD3 genomes AF: 0.949 AC: 105190 AN: 110863 Hom.: 35208 Cov.: 23

Gnomad AFR AF: 0.822

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.996

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.962

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: 0.949 AC: 105239 AN: 110919 Hom.: 35204 Cov.: 23 AF XY: 0.951 AC XY: 31479 AN XY: 33093

African (AFR) AF: 0.822 AC: 25015 AN: 30415

American (AMR) AF: 0.981 AC: 10235 AN: 10430

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 2639 AN: 2641

East Asian (EAS) AF: 1.00 AC: 3528 AN: 3528

South Asian (SAS) AF: 0.999 AC: 2564 AN: 2567

European-Finnish (FIN) AF: 1.00 AC: 5881 AN: 5881

Middle Eastern (MID) AF: 0.995 AC: 216 AN: 217

European-Non Finnish (NFE) AF: 1.00 AC: 53032 AN: 53055

Other (OTH) AF: 0.963 AC: 1453 AN: 1509

Alfa AF: 0.983 Hom.: 92133

Bravo AF: 0.941

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.21
PhyloP100		0.075
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: rs1361038; hg19: chrX-66929686;