13-110457613-T-C

Variant names:

• chr13-110457613-T-C
• rs9515219
• NM_001846.4:c.1432+178T>C

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+178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 694,586 control chromosomes in the GnomAD database, including 109,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25551 hom., cov: 33)
  • Exomes 𝑓: 0.54 (84329 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.902
• Publications: 6 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=-1.0).
• BP6: Variant 13-110457613-T-C is Benign according to our data. Variant chr13-110457613-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231828.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.1432+178T>C		intron	N/A	NP_001837.2
	COL4A2-AS2	NR_171022.1		n.499-26A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.1432+178T>C		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.1513+178T>C		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.1432+178T>C		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86721 AN: 151980 Hom.: 25526 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.512 AC: 76952 AN: 150154 AF XY: 0.517

Gnomad AFR exome AF: 0.632

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.670

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.544 AC: 295019 AN: 542488 Hom.: 84329 Cov.: 3 AF XY: 0.544 AC XY: 159595 AN XY: 293616

African (AFR) AF: 0.633 AC: 9664 AN: 15268

American (AMR) AF: 0.405 AC: 13761 AN: 33960

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 12887 AN: 19296

East Asian (EAS) AF: 0.178 AC: 5399 AN: 30378

South Asian (SAS) AF: 0.480 AC: 29606 AN: 61704

European-Finnish (FIN) AF: 0.445 AC: 20286 AN: 45542

Middle Eastern (MID) AF: 0.689 AC: 2739 AN: 3976

European-Non Finnish (NFE) AF: 0.607 AC: 183936 AN: 303114

Other (OTH) AF: 0.572 AC: 16741 AN: 29250

GnomAD4 genome AF: 0.571 AC: 86797 AN: 152098 Hom.: 25551 Cov.: 33 AF XY: 0.558 AC XY: 41508 AN XY: 74370

African (AFR) AF: 0.627 AC: 26018 AN: 41486

American (AMR) AF: 0.488 AC: 7469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2351 AN: 3464

East Asian (EAS) AF: 0.226 AC: 1160 AN: 5136

South Asian (SAS) AF: 0.459 AC: 2214 AN: 4826

European-Finnish (FIN) AF: 0.429 AC: 4550 AN: 10600

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

European-Non Finnish (NFE) AF: 0.603 AC: 40983 AN: 67976

Other (OTH) AF: 0.578 AC: 1222 AN: 2116

Alfa AF: 0.601 Hom.: 4936

Bravo AF: 0.577

Asia WGS AF: 0.373 AC: 1300 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.56
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9515219; hg19: chr13-111109960; COSMIC: COSV64636519; COSMIC: COSV64636519;