rs4773186

Positions:

• chr13-110459035-G-A
• chr13-110459035-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.1596+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,209,436 control chromosomes in the GnomAD database, including 333,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (43170 hom., cov: 32)
  • Exomes 𝑓: 0.74 (290689 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0100

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110459035-G-A is Benign according to our data. Variant chr13-110459035-G-A is described in ClinVar as [Benign]. Clinvar id is 1293755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.1596+101G>A		intron_variant		ENST00000360467.7
COL4A2-AS2	NR_171022.1	n.266-749C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.1596+101G>A		intron_variant		5	NM_001846.4	P1
COL4A2-AS2	ENST00000458403.2	n.266-749C>T		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000617564.2	c.*20G>A		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113869 AN: 151952 Hom.: 43114 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.738 AC: 780781 AN: 1057364 Hom.: 290689 Cov.: 14 AF XY: 0.737 AC XY: 383136 AN XY: 519802

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.808

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.756

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.750 AC: 113981 AN: 152072 Hom.: 43170 Cov.: 32 AF XY: 0.740 AC XY: 54996 AN XY: 74312

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.764

Alfa AF: 0.766 Hom.: 41402

Bravo AF: 0.762

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
CADD	Benign	0.63
DANN	Benign	0.51

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: rs4773186; hg19: chr13-111111382;