rs75082326

Positions:

• chr13-110449605-A-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.1079-74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,391,932 control chromosomes in the GnomAD database, including 85,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6996 hom., cov: 32)
  • Exomes 𝑓: 0.35 (78779 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.24

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=-0.92).
• BP6: Variant 13-110449605-A-G is Benign according to our data. Variant chr13-110449605-A-G is described in ClinVar as [Benign]. Clinvar id is 1241514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1079-74A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1079-74A>G		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000617564.2	c.336-74A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42334 AN: 151988 Hom.: 6992 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.351 AC: 434702 AN: 1239826 Hom.: 78779 AF XY: 0.351 AC XY: 213992 AN XY: 608806

Gnomad4 AFR exome AF: 0.0966

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.278 AC: 42335 AN: 152106 Hom.: 6996 Cov.: 32 AF XY: 0.279 AC XY: 20766 AN XY: 74338

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.255

Alfa AF: 0.314 Hom.: 1464

Bravo AF: 0.252

Asia WGS AF: 0.273 AC: 953 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

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.20

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: rs75082326; hg19: chr13-111101952; COSMIC: COSV64636531;