chr13-110469370-A-G

Position:

• chr13-110469370-A-G

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.2203+46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,534,760 control chromosomes in the GnomAD database, including 273,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28248 hom., cov: 32)
  • Exomes 𝑓: 0.59 (244819 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.577

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=-0.9).
• BP6: Variant 13-110469370-A-G is Benign according to our data. Variant chr13-110469370-A-G is described in ClinVar as [Benign]. Clinvar id is 1264954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2203+46A>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2203+46A>G		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000494852.2	c.123+46A>G		intron_variant		3		ENSP00000497664

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91182 AN: 151922 Hom.: 28214 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.534 AC: 81631 AN: 152880 Hom.: 22849 AF XY: 0.534 AC XY: 43265 AN XY: 80970

Gnomad AFR exome AF: 0.704

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.301

Gnomad SAS exome AF: 0.487

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.614

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.589 AC: 814817 AN: 1382720 Hom.: 244819 Cov.: 25 AF XY: 0.586 AC XY: 399850 AN XY: 681992

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.600 AC: 91275 AN: 152040 Hom.: 28248 Cov.: 32 AF XY: 0.589 AC XY: 43751 AN XY: 74340

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.606

Alfa AF: 0.561 Hom.: 3168

Bravo AF: 0.606

Asia WGS AF: 0.406 AC: 1413 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	-0.90
CADD	Benign	2.7
DANN	Benign	0.67

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: rs9515229; hg19: chr13-111121717;