rs4773155

Variant names:

• chr13-110318719-A-C
• rs4773155
• NM_001846.4:c.99+10596A>C

Your query was ambiguous. Multiple possible variants found:

• chr13-110318719-A-C
• chr13-110318719-A-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+10596A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,006 control chromosomes in the GnomAD database, including 24,187 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 0.56 (24187 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+10596A>C		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+10596A>C		intron_variant	Intron 3 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85404 AN: 151888 Hom.: 24187 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.562 AC: 85431 AN: 152006 Hom.: 24187 Cov.: 32 AF XY: 0.556 AC XY: 41295 AN XY: 74310

African (AFR) AF: 0.568 AC: 23557 AN: 41444

American (AMR) AF: 0.544 AC: 8319 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2442 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2084 AN: 5156

South Asian (SAS) AF: 0.538 AC: 2592 AN: 4818

European-Finnish (FIN) AF: 0.483 AC: 5091 AN: 10550

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39291 AN: 67966

Other (OTH) AF: 0.608 AC: 1285 AN: 2114

Alfa AF: 0.585 Hom.: 48514

Bravo AF: 0.569

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.59
PhyloP100		0.56
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: rs4773155; hg19: chr13-110971066;