rs3809346

Variant names:

• chr13-110308596-G-A
• rs3809346
• NM_001846.4:c.99+473G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110308596-G-A
• chr13-110308596-G-C
• chr13-110308596-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001846.4(COL4A2):​c.99+473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,856 control chromosomes in the GnomAD database, including 13,349 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13349 hom., cov: 31)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 32 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+473G>A		intron_variant	Intron 3 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.99+473G>A		intron_variant	Intron 3 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63315 AN: 151738 Hom.: 13324 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.417 AC: 63381 AN: 151856 Hom.: 13349 Cov.: 31 AF XY: 0.416 AC XY: 30870 AN XY: 74214

African (AFR) AF: 0.384 AC: 15879 AN: 41402

American (AMR) AF: 0.444 AC: 6786 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3472

East Asian (EAS) AF: 0.389 AC: 1993 AN: 5126

South Asian (SAS) AF: 0.409 AC: 1965 AN: 4802

European-Finnish (FIN) AF: 0.406 AC: 4274 AN: 10522

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29403 AN: 67948

Other (OTH) AF: 0.458 AC: 963 AN: 2102

Alfa AF: 0.421 Hom.: 27805

Bravo AF: 0.417

Asia WGS AF: 0.392 AC: 1363 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.098
DANN	Benign	0.87
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3809346; hg19: chr13-110960943;