rs1983932

Positions:

• chr13-110465874-T-C

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.1979-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,182,920 control chromosomes in the GnomAD database, including 201,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26306 hom., cov: 32)
  • Exomes 𝑓: 0.58 (175438 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22

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=-0.91).
• BP6: Variant 13-110465874-T-C is Benign according to our data. Variant chr13-110465874-T-C is described in ClinVar as [Benign]. Clinvar id is 1293747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1979-129T>C		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1979-129T>C		intron_variant		5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88178 AN: 151926 Hom.: 26282 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.576 AC: 593892 AN: 1030876 Hom.: 175438 AF XY: 0.574 AC XY: 295428 AN XY: 515074

Gnomad4 AFR exome AF: 0.665

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.580 AC: 88259 AN: 152044 Hom.: 26306 Cov.: 32 AF XY: 0.568 AC XY: 42224 AN XY: 74336

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.590

Alfa AF: 0.600 Hom.: 3431

Bravo AF: 0.588

Asia WGS AF: 0.400 AC: 1393 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	-0.91
CADD	Benign	0.18
DANN	Benign	0.21

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: rs1983932; hg19: chr13-111118221; COSMIC: COSV64632519; COSMIC: COSV64632519;