rs1266734

Variant names:

• chrX-108208049-G-A
• rs1266734
• NM_033641.4:c.547-1469C>T

Variant summary

Our verdict is Likely benign. The variant received -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
• 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), Ambry Genetics, ClinGen
• 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=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A6	NM_033641.4	MANE Select	c.547-1469C>T		intron	N/A	NP_378667.1	Q14031-2
	COL4A6	NM_001287758.2		c.547-1469C>T		intron	N/A	NP_001274687.1	A8MXH5
	COL4A6	NM_001847.4		c.550-1469C>T		intron	N/A	NP_001838.2	Q14031-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A6	ENST00000334504.12	TSL:5 MANE Select	c.547-1469C>T		intron	N/A	ENSP00000334733.7	Q14031-2
	COL4A6	ENST00000372216.8	TSL:1	c.550-1469C>T		intron	N/A	ENSP00000361290.4	Q14031-1
	COL4A6	ENST00000621266.4	TSL:1	c.547-1469C>T		intron	N/A	ENSP00000482970.1	A0A087WZY5

Frequencies

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

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

African (AFR) AF: 0.407 AC: 12413 AN: 30464

American (AMR) AF: 0.455 AC: 4734 AN: 10401

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2096 AN: 2619

East Asian (EAS) AF: 0.264 AC: 919 AN: 3487

South Asian (SAS) AF: 0.557 AC: 1448 AN: 2600

European-Finnish (FIN) AF: 0.859 AC: 5067 AN: 5898

Middle Eastern (MID) AF: 0.757 AC: 162 AN: 214

European-Non Finnish (NFE) AF: 0.770 AC: 40568 AN: 52719

Other (OTH) AF: 0.643 AC: 959 AN: 1491

Alfa AF: 0.692 Hom.: 6881

Bravo AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.43
PhyloP100		-0.32
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: rs1266734; hg19: chrX-107451279; COSMIC: COSV57861558;