Variant chrX-108174500-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033641.4(COL4A6):c.3078C>T(p.Gly1026=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,208,104 control chromosomes in the GnomAD database, including 30,479 homozygotes. There are 99,687 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 3298 hom., 8661 hem., cov: 22)

Exomes 𝑓: 0.25 ( 27181 hom. 91026 hem. )

Consequence

COL4A6
NM_033641.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.250

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-108174500-G-A is Benign according to our data. Variant chrX-108174500-G-A is described in ClinVar as [Benign]. Clinvar id is 258271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A6	NM_033641.4 linkuse as main transcript	c.3078C>T	p.Gly1026=	synonymous_variant	31/45	ENST00000334504.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A6	ENST00000334504.12 linkuse as main transcript	c.3078C>T	p.Gly1026=	synonymous_variant	31/45	5	NM_033641.4	P4	Q14031-2

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

29575

AN:

110542

Hom.:

3293

Cov.:

AF XY:

0.263

AC XY:

8631

AN XY:

32848

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.214

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.319

AC:

58149

AN:

182244

Hom.:

8246

AF XY:

0.303

AC XY:

20245

AN XY:

66786

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.606

Gnomad SAS exome

AF:

0.382

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.249

AC:

273774

AN:

1097504

Hom.:

27181

Cov.:

AF XY:

0.251

AC XY:

91026

AN XY:

363012

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.268

AC:

29604

AN:

110600

Hom.:

3298

Cov.:

AF XY:

0.263

AC XY:

8661

AN XY:

32914

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.477

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.613

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.260

Hom.:

5006

Bravo

AF:

0.299

EpiCase

AF:

0.217

EpiControl

AF:

0.212

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Hearing loss, X-linked 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over