rs59905747

Positions:

• chr13-110446698-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.1012-100C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 978,070 control chromosomes in the GnomAD database, including 4,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (748 hom., cov: 33)
  • Exomes 𝑓: 0.084 (4123 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.186

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-110446698-C-G is Benign according to our data. Variant chr13-110446698-C-G is described in ClinVar as [Benign]. Clinvar id is 1231605.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1012-100C>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1012-100C>G		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.269-100C>G		intron_variant
COL4A2	ENST00000650540.1	c.1012-100C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13625 AN: 152104 Hom.: 739 Cov.: 33

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0841 AC: 69451 AN: 825848 Hom.: 4123 AF XY: 0.0818 AC XY: 34751 AN XY: 424912

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.0466

Gnomad4 FIN exome AF: 0.0796

Gnomad4 NFE exome AF: 0.0695

Gnomad4 OTH exome AF: 0.0890

GnomAD4 genome AF: 0.0897 AC: 13661 AN: 152222 Hom.: 748 Cov.: 33 AF XY: 0.0902 AC XY: 6712 AN XY: 74430

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0775 Hom.: 65

Bravo AF: 0.0975

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.88
CADD	Benign	4.3
DANN	Benign	0.30

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: rs59905747; hg19: chr13-111099045; COSMIC: COSV64636511;