13-110206969-GAAA-GAAAA

Position:

• chr13-110206969-GAAA-GAAAA

Variant summary

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

The NM_001845.6(COL4A1):​c.781-79_781-78insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,039,802 control chromosomes in the GnomAD database, including 32 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (27 hom., cov: 18)
  • Exomes 𝑓: 0.12 (5 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.896

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 13-110206969-G-GA is Benign according to our data. Variant chr13-110206969-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 1196465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.781-79_781-78insT		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2	c.781-79_781-78insT		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.781-79_781-78insT		intron_variant		1	NM_001845.6	ENSP00000364979	P1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1741 AN: 139914 Hom.: 26 Cov.: 18

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00237

Gnomad SAS AF: 0.000454

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.00680

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.119 AC: 107049 AN: 899828 Hom.: 5 AF XY: 0.120 AC XY: 54511 AN XY: 453642

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0873

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0872

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.0125 AC: 1751 AN: 139974 Hom.: 27 Cov.: 18 AF XY: 0.0121 AC XY: 822 AN XY: 67862

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.00609

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00238

Gnomad4 SAS AF: 0.000456

Gnomad4 FIN AF: 0.00329

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.0157

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs60585275; hg19: chr13-110859316;