rs76574181

chr13-110210403-G-Achr13-110210403-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001845.6(COL4A1):c.469-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 151,980 control chromosomes in the GnomAD database, including 553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.085 (553 hom., cov: 32)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.55

Genes affected

COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-110210403-G-A is Benign according to our data. Variant chr13-110210403-G-A is described in ClinVar as [Benign]. Clinvar id is 1293365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.469-191C>T		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.469-191C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.469-191C>T		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12909 AN: 151862 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0846

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0851 AC: 12934 AN: 151980 Hom.: 553 Cov.: 32 AF XY: 0.0840 AC XY: 6235 AN XY: 74268

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.0776

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0809

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.0409 Hom.: 22

Bravo AF: 0.0864

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.027
Dann	Benign	0.74

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: rs76574181; hg19: chr13-110862750;