rs4773199

Variant names:

• chr13-110503432-G-A
• rs4773199
• NM_001846.4:c.4089G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110503432-G-A
• chr13-110503432-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001846.4(COL4A2):​c.4089G>A​(p.Ala1363Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,587,136 control chromosomes in the GnomAD database, including 39,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4258 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34755 hom.)
• Consequence: COL4A2 NM_001846.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.423
• Publications: 13 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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 13-110503432-G-A is Benign according to our data. Variant chr13-110503432-G-A is described in ClinVar as Benign. ClinVar VariationId is 311171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.423 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.4089G>A	p.Ala1363Ala	synonymous_variant	Exon 43 of 48	ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.187-504C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.4089G>A	p.Ala1363Ala	synonymous_variant	Exon 43 of 48	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34564 AN: 152024 Hom.: 4257 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.216

GnomAD2 exomes AF: 0.196 AC: 40201 AN: 204648 AF XY: 0.200

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.0538

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.215 AC: 307913 AN: 1434994 Hom.: 34755 Cov.: 34 AF XY: 0.215 AC XY: 152911 AN XY: 711708

African (AFR) AF: 0.304 AC: 10015 AN: 32976

American (AMR) AF: 0.141 AC: 5721 AN: 40448

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 5473 AN: 25540

East Asian (EAS) AF: 0.0338 AC: 1306 AN: 38622

South Asian (SAS) AF: 0.212 AC: 17578 AN: 82994

European-Finnish (FIN) AF: 0.140 AC: 7252 AN: 51782

Middle Eastern (MID) AF: 0.245 AC: 1401 AN: 5708

European-Non Finnish (NFE) AF: 0.225 AC: 246449 AN: 1097666

Other (OTH) AF: 0.215 AC: 12718 AN: 59258

GnomAD4 genome AF: 0.227 AC: 34572 AN: 152142 Hom.: 4258 Cov.: 33 AF XY: 0.220 AC XY: 16350 AN XY: 74390

African (AFR) AF: 0.303 AC: 12600 AN: 41522

American (AMR) AF: 0.182 AC: 2785 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 769 AN: 3472

East Asian (EAS) AF: 0.0439 AC: 227 AN: 5168

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1391 AN: 10612

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15100 AN: 67946

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.231 Hom.: 2173

Bravo AF: 0.233

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephaly 2 Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.55
DANN	Benign	0.75
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4773199; hg19: chr13-111155779; COSMIC: COSV64626170; COSMIC: COSV64626170;