rs4773144

chr13-110308365-A-Gchr13-110308365-A-T

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.99+242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,942 control chromosomes in the GnomAD database, including 13,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.42 (13434 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0400

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=-0.86).
• BP6: Variant 13-110308365-A-G is Benign according to our data. Variant chr13-110308365-A-G is described in ClinVar as [Benign]. Clinvar id is 1254326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.99+242A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.99+242A>G		intron_variant		5	NM_001846.4	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63537 AN: 151822 Hom.: 13410 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.419 AC: 63603 AN: 151942 Hom.: 13434 Cov.: 32 AF XY: 0.417 AC XY: 30991 AN XY: 74256

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.461

Alfa AF: 0.441 Hom.: 19950

Bravo AF: 0.419

Asia WGS AF: 0.392 AC: 1364 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	clinical testing	Invitae	Jan 29, 2024	- -
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	-0.86
Cadd	Benign	6.9
Dann	Benign	0.42

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: rs4773144; hg19: chr13-110960712;