rs388222

Positions:

• chr13-110501812-C-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.3877+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,602,492 control chromosomes in the GnomAD database, including 126,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11610 hom., cov: 31)
  • Exomes 𝑓: 0.39 (114995 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36

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=-0.91).
• BP6: Variant 13-110501812-C-T is Benign according to our data. Variant chr13-110501812-C-T is described in ClinVar as [Benign]. Clinvar id is 1243167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110501812-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3877+28C>T		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3877+28C>T		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000650225.1	n.1532+28C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58381 AN: 151782 Hom.: 11596 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.418 AC: 101692 AN: 243312 Hom.: 22503 AF XY: 0.409 AC XY: 54127 AN XY: 132318

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.410

Gnomad EAS exome AF: 0.641

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.379

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.392 AC: 569018 AN: 1450594 Hom.: 114995 Cov.: 29 AF XY: 0.391 AC XY: 282098 AN XY: 722078

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.385 AC: 58436 AN: 151898 Hom.: 11610 Cov.: 31 AF XY: 0.386 AC XY: 28686 AN XY: 74234

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.388

Alfa AF: 0.384 Hom.: 2322

Bravo AF: 0.398

Asia WGS AF: 0.462 AC: 1605 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	-0.91
CADD	Benign	0.44
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs388222; hg19: chr13-111154159;