rs45612833

Variant names:

• chr13-110446710-G-A
• rs45612833
• NM_001846.4:c.1012-88G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110446710-G-A
• chr13-110446710-G-C
• chr13-110446710-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.1012-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,152,402 control chromosomes in the GnomAD database, including 362,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42904 hom., cov: 32)
  • Exomes 𝑓: 0.80 (319487 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110446710-G-A is Benign according to our data. Variant chr13-110446710-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1012-88G>A		intron_variant	Intron 17 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1012-88G>A		intron_variant	Intron 17 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113567 AN: 151928 Hom.: 42883 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.796 AC: 796621 AN: 1000356 Hom.: 319487 AF XY: 0.796 AC XY: 404552 AN XY: 508520

African (AFR) AF: 0.678 AC: 16357 AN: 24132

American (AMR) AF: 0.663 AC: 27328 AN: 41226

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 18157 AN: 20880

East Asian (EAS) AF: 0.615 AC: 21229 AN: 34520

South Asian (SAS) AF: 0.728 AC: 51818 AN: 71170

European-Finnish (FIN) AF: 0.692 AC: 26383 AN: 38146

Middle Eastern (MID) AF: 0.861 AC: 3775 AN: 4386

European-Non Finnish (NFE) AF: 0.826 AC: 597752 AN: 723238

Other (OTH) AF: 0.793 AC: 33822 AN: 42658

GnomAD4 genome AF: 0.747 AC: 113631 AN: 152046 Hom.: 42904 Cov.: 32 AF XY: 0.740 AC XY: 55005 AN XY: 74332

African (AFR) AF: 0.666 AC: 27606 AN: 41460

American (AMR) AF: 0.734 AC: 11216 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3018 AN: 3472

East Asian (EAS) AF: 0.606 AC: 3112 AN: 5138

South Asian (SAS) AF: 0.720 AC: 3471 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7258 AN: 10582

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55237 AN: 67976

Other (OTH) AF: 0.781 AC: 1644 AN: 2106

Alfa AF: 0.791 Hom.: 9656

Bravo AF: 0.746

Asia WGS AF: 0.652 AC: 2271 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0040
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45612833; hg19: chr13-111099057; COSMIC: COSV107471770;