13-110438677-C-T

Position:

• chr13-110438677-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.912+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,614,062 control chromosomes in the GnomAD database, including 2,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (796 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1851 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.64

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. 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 so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 13-110438677-C-T is Benign according to our data. Variant chr13-110438677-C-T is described in ClinVar as [Benign]. Clinvar id is 311115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110438677-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.912+9C>T		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.912+9C>T		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650540.1	c.912+9C>T		intron_variant				ENSP00000497878.1
COL4A2	ENST00000617564.2	c.168+9C>T		intron_variant		6		ENSP00000481492.3

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12354 AN: 152112 Hom.: 793 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0614

GnomAD3 exomes AF: 0.0564 AC: 14082 AN: 249562 Hom.: 617 AF XY: 0.0563 AC XY: 7622 AN XY: 135398

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.0767

Gnomad SAS exome AF: 0.0925

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.0311

Gnomad OTH exome AF: 0.0429

GnomAD4 exome AF: 0.0403 AC: 58908 AN: 1461832 Hom.: 1851 Cov.: 33 AF XY: 0.0413 AC XY: 30061 AN XY: 727220

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.0412

Gnomad4 ASJ exome AF: 0.0269

Gnomad4 EAS exome AF: 0.0724

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0472

GnomAD4 genome AF: 0.0813 AC: 12374 AN: 152230 Hom.: 796 Cov.: 33 AF XY: 0.0830 AC XY: 6174 AN XY: 74424

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0639

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0608

Alfa AF: 0.0395 Hom.: 303

Bravo AF: 0.0829

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Porencephaly 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.076
DANN	Benign	0.46

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: rs7983979; hg19: chr13-111091024; COSMIC: COSV64631995;