chr13-110388451-A-C

Variant names:

• chr13-110388451-A-C
• rs9515201
• NM_001846.4:c.180+30899A>C

Variant summary

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

The NM_001846.4(COL4A2):​c.180+30899A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,128 control chromosomes in the GnomAD database, including 32,601 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 0.64 (32601 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 37 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.180+30899A>C		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.180+30899A>C		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.180+30899A>C		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.180+30899A>C		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97531 AN: 152010 Hom.: 32595 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.641 AC: 97582 AN: 152128 Hom.: 32601 Cov.: 32 AF XY: 0.650 AC XY: 48323 AN XY: 74372

African (AFR) AF: 0.446 AC: 18482 AN: 41480

American (AMR) AF: 0.748 AC: 11440 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2061 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4568 AN: 5170

South Asian (SAS) AF: 0.773 AC: 3720 AN: 4814

European-Finnish (FIN) AF: 0.741 AC: 7855 AN: 10598

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47145 AN: 67984

Other (OTH) AF: 0.646 AC: 1366 AN: 2116

Alfa AF: 0.679 Hom.: 66593

Bravo AF: 0.635

Asia WGS AF: 0.768 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.52
PhyloP100		2.1
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: rs9515201; hg19: chr13-111040798;