chr13-110211627-CAAAAT-C

Position:

• chr13-110211627-CAAAAT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001845.6(COL4A1):​c.468+15_468+19del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,609,704 control chromosomes in the GnomAD database, including 1,293 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (306 hom., cov: 32)
  • Exomes 𝑓: 0.022 (987 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.06

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 -16 ACMG points.

• BP6: Variant 13-110211627-CAAAAT-C is Benign according to our data. Variant chr13-110211627-CAAAAT-C is described in ClinVar as [Benign]. Clinvar id is 258258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110211627-CAAAAT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.468+15_468+19del		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.468+15_468+19del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.468+15_468+19del		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7157 AN: 152026 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0384 AC: 9526 AN: 248090 Hom.: 471 AF XY: 0.0324 AC XY: 4351 AN XY: 134086

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.0953

Gnomad SAS exome AF: 0.00560

Gnomad FIN exome AF: 0.00560

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.0216 AC: 31492 AN: 1457560 Hom.: 987 AF XY: 0.0205 AC XY: 14868 AN XY: 725078

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.00570

Gnomad4 FIN exome AF: 0.00608

Gnomad4 NFE exome AF: 0.0144

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0472 AC: 7175 AN: 152144 Hom.: 306 Cov.: 32 AF XY: 0.0459 AC XY: 3413 AN XY: 74402

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0970

Gnomad4 SAS AF: 0.00704

Gnomad4 FIN AF: 0.00520

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0295 Hom.: 26

Bravo AF: 0.0580

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Brain small vessel disease 1 with or without ocular anomalies Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Porencephalic cyst Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs3832900; hg19: chr13-110863974;