rs41275110

Positions:

• chr13-110462207-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.1669+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,614,088 control chromosomes in the GnomAD database, including 30,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3087 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27096 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0840

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-110462207-G-A is Benign according to our data. Variant chr13-110462207-G-A is described in ClinVar as [Benign]. Clinvar id is 1232743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110462207-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1669+21G>A		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.265+816C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1669+21G>A		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2-AS2	ENST00000458403.2	n.265+816C>T		intron_variant		2
COL4A2	ENST00000478681.1	n.165+21G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29350 AN: 152120 Hom.: 3090 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.165 AC: 41051 AN: 249442 Hom.: 4031 AF XY: 0.165 AC XY: 22320 AN XY: 135360

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0185

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.186 AC: 271530 AN: 1461850 Hom.: 27096 Cov.: 33 AF XY: 0.184 AC XY: 133790 AN XY: 727226

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.0140

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.193 AC: 29370 AN: 152238 Hom.: 3087 Cov.: 33 AF XY: 0.186 AC XY: 13860 AN XY: 74448

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.213

Alfa AF: 0.203 Hom.: 653

Bravo AF: 0.201

Asia WGS AF: 0.100 AC: 349 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	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.62

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: rs41275110; hg19: chr13-111114554;