rs9588178

Positions:

• chr13-110473229-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.2425+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00924 in 1,385,524 control chromosomes in the GnomAD database, including 867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (488 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (379 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.161

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=-0.87).
• BP6: Variant 13-110473229-G-A is Benign according to our data. Variant chr13-110473229-G-A is described in ClinVar as [Benign]. Clinvar id is 1243791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2425+79G>A		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2425+79G>A		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000494852.2	c.345+79G>A		intron_variant		3		ENSP00000497664

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6928 AN: 152206 Hom.: 485 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0372

GnomAD4 exome AF: 0.00474 AC: 5842 AN: 1233200 Hom.: 379 AF XY: 0.00434 AC XY: 2661 AN XY: 612496

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000487

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000369

Gnomad4 OTH exome AF: 0.0124

GnomAD4 genome AF: 0.0457 AC: 6956 AN: 152324 Hom.: 488 Cov.: 33 AF XY: 0.0430 AC XY: 3205 AN XY: 74488

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0359 Hom.: 40

Bravo AF: 0.0525

Asia WGS AF: 0.00722 AC: 25 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	Jul 10, 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	-0.87
CADD	Benign	2.1
DANN	Benign	0.55

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: rs9588178; hg19: chr13-111125576;