rs1266754

Variant names:

• chrX-108250180-C-T
• rs1266754
• NM_033641.4:c.145-28806G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B.

Score: -4 - Likely Benign

-4

BP4_Strong

The NM_033641.4(COL4A6):​c.145-28806G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.63 (16932 hom., 20210 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: COL4A6 NM_033641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A6	NM_033641.4	c.145-28806G>A		intron_variant	Intron 3 of 44	ENST00000334504.12	NP_378667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A6	ENST00000334504.12	c.145-28806G>A		intron_variant	Intron 3 of 44	5	NM_033641.4	ENSP00000334733.7

Frequencies

GnomAD3 genomes AF: 0.631 AC: 69271 AN: 109849 Hom.: 16937 Cov.: 22

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.643

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: 0.630 AC: 69260 AN: 109899 Hom.: 16932 Cov.: 22 AF XY: 0.626 AC XY: 20210 AN XY: 32283

African (AFR) AF: 0.403 AC: 12171 AN: 30194

American (AMR) AF: 0.465 AC: 4815 AN: 10358

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2118 AN: 2609

East Asian (EAS) AF: 0.268 AC: 919 AN: 3434

South Asian (SAS) AF: 0.552 AC: 1376 AN: 2494

European-Finnish (FIN) AF: 0.862 AC: 5017 AN: 5817

Middle Eastern (MID) AF: 0.765 AC: 166 AN: 217

European-Non Finnish (NFE) AF: 0.784 AC: 41240 AN: 52602

Other (OTH) AF: 0.649 AC: 975 AN: 1503

Alfa AF: 0.712 Hom.: 7617

Bravo AF: 0.591

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		0.47
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: rs1266754; hg19: chrX-107493410;