rs2064722

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
COL4A6	NM_033641.4	c.64-56966T>C		intron_variant		ENST00000334504.12	NP_378667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A6	ENST00000334504.12	c.64-56966T>C		intron_variant		5	NM_033641.4	ENSP00000334733	P4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 40759 AN: 109997 Hom.: 6745 Cov.: 22 AF XY: 0.362 AC XY: 11697 AN XY: 32349

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

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.348

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2064722; hg19: chrX-107611024;