rs1475438

Positions:

• chr13-110480473-G-A

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.2758+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,412,166 control chromosomes in the GnomAD database, including 331,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36091 hom., cov: 33)
  • Exomes 𝑓: 0.68 (295251 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.801

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=-0.93).
• BP6: Variant 13-110480473-G-A is Benign according to our data. Variant chr13-110480473-G-A is described in ClinVar as [Benign]. Clinvar id is 1231053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2758+83G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2758+83G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000483683.2	n.388+83G>A		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000650225.1	n.413+83G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104348 AN: 152000 Hom.: 36055 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.682 AC: 859662 AN: 1260048 Hom.: 295251 AF XY: 0.686 AC XY: 422765 AN XY: 616054

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.719

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.687 AC: 104443 AN: 152118 Hom.: 36091 Cov.: 33 AF XY: 0.693 AC XY: 51492 AN XY: 74356

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.698

Alfa AF: 0.671 Hom.: 6856

Bravo AF: 0.679

Asia WGS AF: 0.812 AC: 2824 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	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.38

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: rs1475438; hg19: chr13-111132820;