13-110429711-T-C

Position:

• chr13-110429711-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.478-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,082 control chromosomes in the GnomAD database, including 19,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.51 (19911 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.102

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 13-110429711-T-C is Benign according to our data. Variant chr13-110429711-T-C is described in ClinVar as [Benign]. Clinvar id is 1271252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.478-174T>C		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.478-174T>C		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000619688.2	c.*1077T>C		3_prime_UTR_variant	3/3			ENSP00000496868
COL4A2	ENST00000650540.1	c.478-174T>C		intron_variant				ENSP00000497878

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77233 AN: 151964 Hom.: 19891 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77314 AN: 152082 Hom.: 19911 Cov.: 33 AF XY: 0.505 AC XY: 37557 AN XY: 74342

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.507

Alfa AF: 0.498 Hom.: 42015

Bravo AF: 0.515

Asia WGS AF: 0.443 AC: 1546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs4512966; hg19: chr13-111082058;