rs41275110

Variant names:

• chr13-110462207-G-A
• rs41275110
• NM_001846.4:c.1669+21G>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.1669+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,614,088 control chromosomes in the GnomAD database, including 30,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3087 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27096 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0840
• Publications: 8 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=-0.86).
• BP6: Variant 13-110462207-G-A is Benign according to our data. Variant chr13-110462207-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1669+21G>A		intron_variant	Intron 23 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.265+816C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1669+21G>A		intron_variant	Intron 23 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29350 AN: 152120 Hom.: 3090 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.165 AC: 41051 AN: 249442 AF XY: 0.165

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0185

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.186 AC: 271530 AN: 1461850 Hom.: 27096 Cov.: 33 AF XY: 0.184 AC XY: 133790 AN XY: 727226

African (AFR) AF: 0.235 AC: 7873 AN: 33478

American (AMR) AF: 0.124 AC: 5531 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7313 AN: 26136

East Asian (EAS) AF: 0.0140 AC: 556 AN: 39700

South Asian (SAS) AF: 0.109 AC: 9382 AN: 86258

European-Finnish (FIN) AF: 0.133 AC: 7099 AN: 53414

Middle Eastern (MID) AF: 0.329 AC: 1896 AN: 5768

European-Non Finnish (NFE) AF: 0.198 AC: 220259 AN: 1111982

Other (OTH) AF: 0.192 AC: 11621 AN: 60394

GnomAD4 genome AF: 0.193 AC: 29370 AN: 152238 Hom.: 3087 Cov.: 33 AF XY: 0.186 AC XY: 13860 AN XY: 74448

African (AFR) AF: 0.233 AC: 9664 AN: 41526

American (AMR) AF: 0.185 AC: 2835 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5184

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.122 AC: 1297 AN: 10602

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13195 AN: 68002

Other (OTH) AF: 0.213 AC: 450 AN: 2116

Alfa AF: 0.203 Hom.: 653

Bravo AF: 0.201

Asia WGS AF: 0.100 AC: 349 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

- -

Jul 09, 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	-0.86
CADD	Benign	2.3
DANN	Benign	0.62
PhyloP100		0.084
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: rs41275110; hg19: chr13-111114554;