rs5918764

Variant names:

• chrX-67717865-A-G
• rs5918764
• NM_000044.6:c.2318+243A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-67717865-A-G
• chrX-67717865-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000044.6(AR):​c.2318+243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (27028 hom., 28027 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: AR NM_000044.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.760
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P
• Kennedy disease

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant X-67717865-A-G is Benign according to our data. Variant chrX-67717865-A-G is described in ClinVar as Benign. ClinVar VariationId is 1183563.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000044.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AR	NM_000044.6	MANE Select	c.2318+243A>G		intron	N/A	NP_000035.2
	AR	NM_001011645.3		c.722+243A>G		intron	N/A	NP_001011645.1	Q9NUA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AR	ENST00000374690.9	TSL:1 MANE Select	c.2318+243A>G		intron	N/A	ENSP00000363822.3	P10275-1
	AR	ENST00000396044.8	TSL:1	c.2174-5821A>G		intron	N/A	ENSP00000379359.3	F5GZG9
	AR	ENST00000396043.4	TSL:1	n.*666+243A>G		intron	N/A	ENSP00000379358.4	A0A7I2PS51

Frequencies

GnomAD3 genomes AF: 0.818 AC: 91305 AN: 111618 Hom.: 27034 Cov.: 24

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.919

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.873

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: 0.818 AC: 91338 AN: 111672 Hom.: 27028 Cov.: 24 AF XY: 0.828 AC XY: 28027 AN XY: 33856

African (AFR) AF: 0.524 AC: 16101 AN: 30703

American (AMR) AF: 0.931 AC: 9852 AN: 10579

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 2514 AN: 2645

East Asian (EAS) AF: 0.999 AC: 3516 AN: 3518

South Asian (SAS) AF: 0.944 AC: 2511 AN: 2660

European-Finnish (FIN) AF: 0.937 AC: 5659 AN: 6042

Middle Eastern (MID) AF: 0.916 AC: 196 AN: 214

European-Non Finnish (NFE) AF: 0.923 AC: 49038 AN: 53103

Other (OTH) AF: 0.876 AC: 1337 AN: 1527

Alfa AF: 0.887 Hom.: 17069

Bravo AF: 0.809

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.54
PhyloP100		-0.76
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5918764;

hg19: chrX-66937707;