rs403839

Variant names:

• chr13-110491974-G-A
• rs403839
• NM_001846.4:c.3455-96G>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.3455-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,070,718 control chromosomes in the GnomAD database, including 6,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1018 hom., cov: 33)
  • Exomes 𝑓: 0.11 (5775 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0150

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=-0.86).
• BP6: Variant 13-110491974-G-A is Benign according to our data. Variant chr13-110491974-G-A is described in ClinVar as [Benign]. Clinvar id is 1289440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3455-96G>A		intron_variant	Intron 37 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3455-96G>A		intron_variant	Intron 37 of 47	5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650225.1	n.1110-96G>A		intron_variant	Intron 8 of 18

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17339 AN: 152088 Hom.: 1015 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0969

GnomAD4 exome AF: 0.108 AC: 99269 AN: 918512 Hom.: 5775 AF XY: 0.107 AC XY: 48903 AN XY: 458916

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.0668

Gnomad4 FIN exome AF: 0.0840

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.114 AC: 17359 AN: 152206 Hom.: 1018 Cov.: 33 AF XY: 0.113 AC XY: 8375 AN XY: 74418

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0662

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.114 Hom.: 149

Bravo AF: 0.119

Asia WGS AF: 0.106 AC: 366 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.63

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: rs403839; hg19: chr13-111144321; COSMIC: COSV64627356;