rs414881

Variant names:

• chr13-110504064-G-A
• rs414881
• NM_001846.4:c.4285+71G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110504064-G-A
• chr13-110504064-G-T

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.4285+71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,558,194 control chromosomes in the GnomAD database, including 182,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15552 hom., cov: 32)
  • Exomes 𝑓: 0.48 (166635 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.40
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-110504064-G-A is Benign according to our data. Variant chr13-110504064-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.4285+71G>A		intron_variant	Intron 44 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.187-1136C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.4285+71G>A		intron_variant	Intron 44 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68092 AN: 151878 Hom.: 15532 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.483 AC: 679840 AN: 1406198 Hom.: 166635 Cov.: 23 AF XY: 0.485 AC XY: 340024 AN XY: 701306

African (AFR) AF: 0.344 AC: 11057 AN: 32146

American (AMR) AF: 0.537 AC: 23205 AN: 43248

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 11126 AN: 24786

East Asian (EAS) AF: 0.616 AC: 24302 AN: 39440

South Asian (SAS) AF: 0.536 AC: 44743 AN: 83438

European-Finnish (FIN) AF: 0.446 AC: 23411 AN: 52504

Middle Eastern (MID) AF: 0.443 AC: 2452 AN: 5536

European-Non Finnish (NFE) AF: 0.480 AC: 511985 AN: 1066718

Other (OTH) AF: 0.472 AC: 27559 AN: 58382

GnomAD4 genome AF: 0.448 AC: 68151 AN: 151996 Hom.: 15552 Cov.: 32 AF XY: 0.450 AC XY: 33403 AN XY: 74288

African (AFR) AF: 0.355 AC: 14737 AN: 41520

American (AMR) AF: 0.470 AC: 7194 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3163 AN: 5116

South Asian (SAS) AF: 0.528 AC: 2545 AN: 4816

European-Finnish (FIN) AF: 0.440 AC: 4666 AN: 10596

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32528 AN: 67864

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.459 Hom.: 3905

Bravo AF: 0.449

Asia WGS AF: 0.562 AC: 1955 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	-0.82
CADD	Benign	0.20
DANN	Benign	0.77
PhyloP100		-3.4
PromoterAI		-0.13	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs414881; hg19: chr13-111156411; COSMIC: COSV64628851; COSMIC: COSV64628851;