13-110445763-C-T

Position:

• chr13-110445763-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.958-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,560,462 control chromosomes in the GnomAD database, including 545,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53167 hom., cov: 32)
  • Exomes 𝑓: 0.83 (492104 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12

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=-0.92).
• BP6: Variant 13-110445763-C-T is Benign according to our data. Variant chr13-110445763-C-T is described in ClinVar as [Benign]. Clinvar id is 1174325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.958-66C>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.958-66C>T		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000617564.2	c.215-66C>T		intron_variant				ENSP00000481492
COL4A2	ENST00000650540.1	c.958-66C>T		intron_variant				ENSP00000497878

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126886 AN: 152076 Hom.: 53130 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.835 AC: 1175399 AN: 1408268 Hom.: 492104 AF XY: 0.835 AC XY: 587909 AN XY: 703700

Gnomad4 AFR exome AF: 0.862

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.836

GnomAD4 genome AF: 0.834 AC: 126975 AN: 152194 Hom.: 53167 Cov.: 32 AF XY: 0.830 AC XY: 61718 AN XY: 74394

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.840

Alfa AF: 0.847 Hom.: 11697

Bravo AF: 0.832

Asia WGS AF: 0.729 AC: 2538 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.31

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: rs7489705; hg19: chr13-111098110;