rs35638294

chr13-110209273-T-TAAAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001845.6(COL4A1):c.651+118_651+119insCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 794,442 control chromosomes in the GnomAD database, including 26,206 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4891 hom., cov: 24)
  • Exomes 𝑓: 0.25 (21315 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 -10 ACMG points.

• BP6: Variant 13-110209273-T-TAAAG is Benign according to our data. Variant chr13-110209273-T-TAAAG is described in ClinVar as [Benign]. Clinvar id is 1181737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.651+118_651+119insCTTT		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.651+118_651+119insCTTT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.651+118_651+119insCTTT		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37330 AN: 151918 Hom.: 4884 Cov.: 24

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.247 AC: 158376 AN: 642406 Hom.: 21315 AF XY: 0.246 AC XY: 85013 AN XY: 345438

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.319

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.0304

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.246 AC: 37370 AN: 152036 Hom.: 4891 Cov.: 24 AF XY: 0.248 AC XY: 18448 AN XY: 74314

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.217

Alfa AF: 0.247 Hom.: 278

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35638294; hg19: chr13-110861620;