rs9515218

Variant names:

• chr13-110457512-A-G
• rs9515218
• NM_001846.4:c.1432+77A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-110457512-A-G
• chr13-110457512-A-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.1432+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 847,884 control chromosomes in the GnomAD database, including 137,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25659 hom., cov: 32)
  • Exomes 𝑓: 0.55 (111857 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39
• Publications: 10 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=-0.92).
• BP6: Variant 13-110457512-A-G is Benign according to our data. Variant chr13-110457512-A-G is described in ClinVar as Benign. ClinVar VariationId is 1249370.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.1432+77A>G		intron_variant	Intron 21 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.561+13T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1432+77A>G		intron_variant	Intron 21 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86896 AN: 151944 Hom.: 25634 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.579

GnomAD2 exomes AF: 0.520 AC: 97398 AN: 187482 AF XY: 0.524

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.557

GnomAD4 exome AF: 0.554 AC: 385330 AN: 695822 Hom.: 111857 Cov.: 9 AF XY: 0.553 AC XY: 205069 AN XY: 370836

African (AFR) AF: 0.632 AC: 11577 AN: 18306

American (AMR) AF: 0.399 AC: 15412 AN: 38594

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 13903 AN: 20854

East Asian (EAS) AF: 0.177 AC: 6022 AN: 33944

South Asian (SAS) AF: 0.478 AC: 32005 AN: 66960

European-Finnish (FIN) AF: 0.444 AC: 22408 AN: 50442

Middle Eastern (MID) AF: 0.688 AC: 2966 AN: 4308

European-Non Finnish (NFE) AF: 0.611 AC: 261080 AN: 427534

Other (OTH) AF: 0.572 AC: 19957 AN: 34880

GnomAD4 genome AF: 0.572 AC: 86971 AN: 152062 Hom.: 25659 Cov.: 32 AF XY: 0.559 AC XY: 41553 AN XY: 74312

African (AFR) AF: 0.628 AC: 26047 AN: 41494

American (AMR) AF: 0.489 AC: 7480 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2357 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1159 AN: 5142

South Asian (SAS) AF: 0.458 AC: 2206 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4552 AN: 10576

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41117 AN: 67956

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

Alfa AF: 0.594 Hom.: 6737

Bravo AF: 0.578

Asia WGS AF: 0.374 AC: 1304 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	-0.92
CADD	Benign	0.24
DANN	Benign	0.30
PhyloP100		-1.4
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: rs9515218; hg19: chr13-111109859; COSMIC: COSV107471704; COSMIC: COSV107471704;