13-110458696-G-A

Variant names:

• chr13-110458696-G-A
• rs9521782
• NM_001846.4:c.1433-75G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.1433-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,581,270 control chromosomes in the GnomAD database, including 267,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25349 hom., cov: 31)
  • Exomes 𝑓: 0.57 (242622 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.54
• Publications: 7 publications found

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:39849): (COL4A2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 13-110458696-G-A is Benign according to our data. Variant chr13-110458696-G-A is described in ClinVar as Benign. ClinVar VariationId is 1291185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1433-75G>A		intron_variant	Intron 21 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.266-410C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1433-75G>A		intron_variant	Intron 21 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86259 AN: 151372 Hom.: 25324 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.575 AC: 821924 AN: 1429780 Hom.: 242622 AF XY: 0.573 AC XY: 407464 AN XY: 711038

African (AFR) AF: 0.639 AC: 20925 AN: 32742

American (AMR) AF: 0.391 AC: 16784 AN: 42882

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 16232 AN: 24490

East Asian (EAS) AF: 0.184 AC: 7256 AN: 39472

South Asian (SAS) AF: 0.477 AC: 39417 AN: 82674

European-Finnish (FIN) AF: 0.445 AC: 23029 AN: 51762

Middle Eastern (MID) AF: 0.674 AC: 3786 AN: 5620

European-Non Finnish (NFE) AF: 0.605 AC: 660572 AN: 1091012

Other (OTH) AF: 0.574 AC: 33923 AN: 59126

GnomAD4 genome AF: 0.570 AC: 86335 AN: 151490 Hom.: 25349 Cov.: 31 AF XY: 0.557 AC XY: 41241 AN XY: 74022

African (AFR) AF: 0.628 AC: 25893 AN: 41242

American (AMR) AF: 0.488 AC: 7437 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2352 AN: 3464

East Asian (EAS) AF: 0.225 AC: 1155 AN: 5138

South Asian (SAS) AF: 0.457 AC: 2199 AN: 4808

European-Finnish (FIN) AF: 0.426 AC: 4486 AN: 10522

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40774 AN: 67766

Other (OTH) AF: 0.578 AC: 1220 AN: 2110

Alfa AF: 0.599 Hom.: 4019

Bravo AF: 0.577

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.55
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9521782; hg19: chr13-111111043; COSMIC: COSV64632006; COSMIC: COSV64632006;