13-110457613-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):c.1432+178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 694,586 control chromosomes in the GnomAD database, including 109,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25551 hom., cov: 33)
  • Exomes 𝑓: 0.54 (84329 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.902

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]

COL4A2-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 13-110457613-T-C is Benign according to our data. Variant chr13-110457613-T-C is described in ClinVar as [Benign]. Clinvar id is 1231828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1432+178T>C		intron_variant		ENST00000360467.7
COL4A2-AS2	NR_171022.1	n.499-26A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1432+178T>C		intron_variant		5	NM_001846.4	P1
COL4A2-AS2	ENST00000458403.2	n.499-26A>G		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000617564.2	c.689+178T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86721 AN: 151980 Hom.: 25526 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.578

GnomAD3 exomes AF: 0.512 AC: 76952 AN: 150154 Hom.: 20871 AF XY: 0.517 AC XY: 41715 AN XY: 80694

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.670

Gnomad EAS exome AF: 0.236

Gnomad SAS exome AF: 0.485

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.544 AC: 295019 AN: 542488 Hom.: 84329 Cov.: 3 AF XY: 0.544 AC XY: 159595 AN XY: 293616

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.668

Gnomad4 EAS exome AF: 0.178

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.571 AC: 86797 AN: 152098 Hom.: 25551 Cov.: 33 AF XY: 0.558 AC XY: 41508 AN XY: 74370

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.578

Alfa AF: 0.601 Hom.: 4936

Bravo AF: 0.577

Asia WGS AF: 0.373 AC: 1300 AN: 3478

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

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.7
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9515219; hg19: chr13-111109960; COSMIC: COSV64636519; COSMIC: COSV64636519;