rs1204040

Variant names:

• chrX-67565906-C-A
• rs1204040
• NM_000044.6:c.1616+19144C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-67565906-C-A
• chrX-67565906-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000044.6(AR):​c.1616+19144C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 110,733 control chromosomes in the GnomAD database, including 4,493 homozygotes. There are 8,046 hemizygotes in GnomAD. 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 0.26 (4493 hom., 8046 hem., cov: 22)
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6	c.1616+19144C>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+19144C>A		intron_variant	Intron 1 of 7	1	NM_000044.6	ENSP00000363822.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 29306 AN: 110683 Hom.: 4493 Cov.: 22

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00142

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.265 AC: 29339 AN: 110733 Hom.: 4493 Cov.: 22 AF XY: 0.244 AC XY: 8046 AN XY: 33043

African (AFR) AF: 0.589 AC: 17853 AN: 30313

American (AMR) AF: 0.139 AC: 1453 AN: 10446

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 297 AN: 2631

East Asian (EAS) AF: 0.00143 AC: 5 AN: 3507

South Asian (SAS) AF: 0.0793 AC: 209 AN: 2636

European-Finnish (FIN) AF: 0.113 AC: 674 AN: 5962

Middle Eastern (MID) AF: 0.188 AC: 40 AN: 213

European-Non Finnish (NFE) AF: 0.159 AC: 8387 AN: 52844

Other (OTH) AF: 0.227 AC: 341 AN: 1500

Alfa AF: 0.0744 Hom.: 347

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.51
DANN	Benign	0.31
PhyloP100		-0.20
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: rs1204040; hg19: chrX-66785748;