rs963337

chrX-108285009-A-GchrX-108285009-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.144+25739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 110,784 control chromosomes in the GnomAD database, including 3,217 homozygotes. There are 8,641 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 (3217 hom., 8641 hem., cov: 23)
• Consequence: COL4A6 NM_033641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A6	NM_033641.4	c.144+25739T>C		intron_variant		ENST00000334504.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A6	ENST00000334504.12	c.144+25739T>C		intron_variant		5	NM_033641.4	P4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 29243 AN: 110726 Hom.: 3212 Cov.: 23 AF XY: 0.261 AC XY: 8603 AN XY: 32984

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.264 AC: 29283 AN: 110784 Hom.: 3217 Cov.: 23 AF XY: 0.261 AC XY: 8641 AN XY: 33052

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.260

Alfa AF: 0.235 Hom.: 4753

Bravo AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.6
Dann	Benign	0.68

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: rs963337; hg19: chrX-107528239;