Variant X-108159454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033641.4(COL4A6):c.4812+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,209,962 control chromosomes in the GnomAD database, including 993 homozygotes. There are 18,294 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 126 hom., 1661 hem., cov: 23)

Exomes 𝑓: 0.046 ( 867 hom. 16633 hem. )

Consequence

COL4A6
NM_033641.4 splice_region, intron

Scores

Splicing: ADA: 0.00009680

Clinical Significance

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

Conservation

PhyloP100: 0.220

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 -20 ACMG points.

BP4

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

BP6

Variant X-108159454-G-A is Benign according to our data. Variant chrX-108159454-G-A is described in ClinVar as [Benign]. Clinvar id is 258280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.086 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.4812+8C>T		splice_region_variant, intron_variant		ENST00000334504.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A6	ENST00000334504.12 linkuse as main transcript	c.4812+8C>T		splice_region_variant, intron_variant		5	NM_033641.4	P4	Q14031-2

Frequencies

GnomAD3 genomes

AF:

0.0510

AC:

5729

AN:

112291

Hom.:

126

Cov.:

AF XY:

0.0481

AC XY:

1656

AN XY:

34443

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0385

Gnomad EAS

AF:

0.0944

Gnomad SAS

AF:

0.0384

Gnomad FIN

AF:

0.0342

Gnomad MID

AF:

0.0549

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0502

AC:

9074

AN:

180829

Hom.:

174

AF XY:

0.0477

AC XY:

3150

AN XY:

66099

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0399

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0380

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0484

Gnomad OTH exome

AF:

0.0524

GnomAD4 exome

AF:

0.0461

AC:

50593

AN:

1097619

Hom.:

867

Cov.:

AF XY:

0.0458

AC XY:

16633

AN XY:

363023

show subpopulations

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.0455

Gnomad4 ASJ exome

AF:

0.0407

Gnomad4 EAS exome

AF:

0.0715

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0376

Gnomad4 NFE exome

AF:

0.0455

Gnomad4 OTH exome

AF:

0.0494

GnomAD4 genome

AF:

0.0511

AC:

5736

AN:

112343

Hom.:

126

Cov.:

AF XY:

0.0481

AC XY:

1661

AN XY:

34505

show subpopulations

Gnomad4 AFR

AF:

0.0561

Gnomad4 AMR

AF:

0.0425

Gnomad4 ASJ

AF:

0.0385

Gnomad4 EAS

AF:

0.0944

Gnomad4 SAS

AF:

0.0386

Gnomad4 FIN

AF:

0.0342

Gnomad4 NFE

AF:

0.0485

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0501

Hom.:

508

Bravo

AF:

0.0530

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	PreventionGenetics, part of Exact Sciences	-	- -
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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 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

6.2

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000097

dbscSNV1_RF

Benign

0.0080

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