rs11839527

Positions:

• chr13-110485141-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.3025+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 955,290 control chromosomes in the GnomAD database, including 8,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1122 hom., cov: 31)
  • Exomes 𝑓: 0.13 (7264 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 13-110485141-G-A is Benign according to our data. Variant chr13-110485141-G-A is described in ClinVar as [Benign]. Clinvar id is 1271478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3025+114G>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.3025+114G>A		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650225.1	n.680+114G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18825 AN: 152030 Hom.: 1122 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.131 AC: 105501 AN: 803142 Hom.: 7264 AF XY: 0.131 AC XY: 52022 AN XY: 398418

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0962

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.124 AC: 18850 AN: 152148 Hom.: 1122 Cov.: 31 AF XY: 0.124 AC XY: 9228 AN XY: 74378

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.118

Alfa AF: 0.129 Hom.: 1249

Bravo AF: 0.126

Asia WGS AF: 0.114 AC: 395 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	-1.1
CADD	Benign	0.52
DANN	Benign	0.69

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: rs11839527; hg19: chr13-111137488;