rs9559813

chr13-110469097-C-Achr13-110469097-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.2096-120C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,123,912 control chromosomes in the GnomAD database, including 123,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19563 hom., cov: 33)
  • Exomes 𝑓: 0.46 (104332 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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=-0.85).
• BP6: Variant 13-110469097-C-A is Benign according to our data. Variant chr13-110469097-C-A is described in ClinVar as [Benign]. Clinvar id is 1221711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2096-120C>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2096-120C>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000494852.2	c.16-120C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74954 AN: 151898 Hom.: 19534 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.458 AC: 444899 AN: 971896 Hom.: 104332 AF XY: 0.455 AC XY: 220448 AN XY: 484670

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.494 AC: 75043 AN: 152016 Hom.: 19563 Cov.: 33 AF XY: 0.482 AC XY: 35830 AN XY: 74298

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.480

Alfa AF: 0.451 Hom.: 4271

Bravo AF: 0.499

Asia WGS AF: 0.298 AC: 1037 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	-0.85
Cadd	Benign	0.78
Dann	Benign	0.54

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: rs9559813; hg19: chr13-111121444;