rs2064722

Variant names:

• chrX-108367794-A-G
• rs2064722
• NM_033641.4:c.64-56966T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-108367794-A-G
• chrX-108367794-A-T

Variant summary

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

The NM_033641.4(COL4A6):​c.64-56966T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 110,051 control chromosomes in the GnomAD database, including 6,744 homozygotes. There are 11,752 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 0.37 (6744 hom., 11752 hem., cov: 22)
• Consequence: COL4A6 NM_033641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 1 publications found

Genes affected

COL4A6 (HGNC:2208): (collagen type IV alpha 6 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]

COL4A6 Gene-Disease associations (from GenCC):

• hearing loss, X-linked 6

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• X-linked nonsyndromic hearing loss

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• premature ovarian failure 1

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A6	NM_033641.4	c.64-56966T>C		intron_variant	Intron 2 of 44	ENST00000334504.12	NP_378667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A6	ENST00000334504.12	c.64-56966T>C		intron_variant	Intron 2 of 44	5	NM_033641.4	ENSP00000334733.7

Frequencies

GnomAD3 genomes AF: 0.371 AC: 40759 AN: 109997 Hom.: 6745 Cov.: 22

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.371 AC: 40812 AN: 110051 Hom.: 6744 Cov.: 22 AF XY: 0.363 AC XY: 11752 AN XY: 32413

African (AFR) AF: 0.585 AC: 17647 AN: 30176

American (AMR) AF: 0.526 AC: 5414 AN: 10289

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 497 AN: 2628

East Asian (EAS) AF: 0.727 AC: 2513 AN: 3455

South Asian (SAS) AF: 0.400 AC: 1035 AN: 2587

European-Finnish (FIN) AF: 0.154 AC: 904 AN: 5879

Middle Eastern (MID) AF: 0.218 AC: 47 AN: 216

European-Non Finnish (NFE) AF: 0.228 AC: 12023 AN: 52647

Other (OTH) AF: 0.348 AC: 523 AN: 1501

Alfa AF: 0.317 Hom.: 2338

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		0.33
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: rs2064722; hg19: chrX-107611024;