rs1266734

Positions:

• chrX-108208049-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033641.4(COL4A6):​c.547-1469C>T 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 0.62 (16393 hom., 20460 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: COL4A6 NM_033641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A6	NM_033641.4	c.547-1469C>T		intron_variant		ENST00000334504.12	NP_378667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A6	ENST00000334504.12	c.547-1469C>T		intron_variant		5	NM_033641.4	ENSP00000334733	P4

Frequencies

GnomAD3 genomes AF: 0.623 AC: 68830 AN: 110515 Hom.: 16397 Cov.: 23 AF XY: 0.623 AC XY: 20454 AN XY: 32849

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.638

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: 0.622 AC: 68825 AN: 110566 Hom.: 16393 Cov.: 23 AF XY: 0.622 AC XY: 20460 AN XY: 32910

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.643

Alfa AF: 0.692 Hom.: 6881

Bravo AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.43

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: rs1266734; hg19: chrX-107451279; COSMIC: COSV57861558;