13-110447919-A-G

Variant names:

• chr13-110447919-A-G
• rs4132608
• NM_001846.4:c.1078+1055A>G

Variant summary

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

The NM_001846.4(COL4A2):​c.1078+1055A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,182 control chromosomes in the GnomAD database, including 43,201 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 0.75 (43201 hom., cov: 34)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1078+1055A>G		intron_variant	Intron 18 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1078+1055A>G		intron_variant	Intron 18 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113990 AN: 152064 Hom.: 43173 Cov.: 34

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.750 AC: 114070 AN: 152182 Hom.: 43201 Cov.: 34 AF XY: 0.755 AC XY: 56155 AN XY: 74402

African (AFR) AF: 0.651 AC: 27006 AN: 41502

American (AMR) AF: 0.776 AC: 11873 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2402 AN: 3470

East Asian (EAS) AF: 0.947 AC: 4904 AN: 5176

South Asian (SAS) AF: 0.842 AC: 4061 AN: 4824

European-Finnish (FIN) AF: 0.799 AC: 8459 AN: 10592

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52943 AN: 68010

Other (OTH) AF: 0.741 AC: 1562 AN: 2108

Alfa AF: 0.760 Hom.: 57834

Bravo AF: 0.740

Asia WGS AF: 0.870 AC: 3025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.53
DANN	Benign	0.37
PhyloP100		-2.2
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: rs4132608; hg19: chr13-111100266;