rs1475438

Variant names:

• chr13-110480473-G-A
• rs1475438
• NM_001846.4:c.2758+83G>A

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.2758+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,412,166 control chromosomes in the GnomAD database, including 331,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (36091 hom., cov: 33)
  • Exomes 𝑓: 0.68 (295251 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.801
• 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=-0.93).
• BP6: Variant 13-110480473-G-A is Benign according to our data. Variant chr13-110480473-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2758+83G>A		intron_variant	Intron 31 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2758+83G>A		intron_variant	Intron 31 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104348 AN: 152000 Hom.: 36055 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.682 AC: 859662 AN: 1260048 Hom.: 295251 AF XY: 0.686 AC XY: 422765 AN XY: 616054

African (AFR) AF: 0.638 AC: 17734 AN: 27796

American (AMR) AF: 0.780 AC: 18846 AN: 24168

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 13813 AN: 19330

East Asian (EAS) AF: 0.878 AC: 30669 AN: 34946

South Asian (SAS) AF: 0.828 AC: 52916 AN: 63894

European-Finnish (FIN) AF: 0.719 AC: 29451 AN: 40972

Middle Eastern (MID) AF: 0.684 AC: 3429 AN: 5016

European-Non Finnish (NFE) AF: 0.662 AC: 656211 AN: 991312

Other (OTH) AF: 0.695 AC: 36593 AN: 52614

GnomAD4 genome AF: 0.687 AC: 104443 AN: 152118 Hom.: 36091 Cov.: 33 AF XY: 0.693 AC XY: 51492 AN XY: 74356

African (AFR) AF: 0.651 AC: 27012 AN: 41498

American (AMR) AF: 0.743 AC: 11356 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2412 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4317 AN: 5152

South Asian (SAS) AF: 0.838 AC: 4044 AN: 4828

European-Finnish (FIN) AF: 0.727 AC: 7698 AN: 10584

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45476 AN: 67974

Other (OTH) AF: 0.698 AC: 1475 AN: 2112

Alfa AF: 0.671 Hom.: 6856

Bravo AF: 0.679

Asia WGS AF: 0.812 AC: 2824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		-0.80
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: rs1475438; hg19: chr13-111132820;