13-110319533-C-T

Variant names:

• chr13-110319533-C-T
• rs9555687
• NM_001846.4:c.99+11410C>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+11410C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,004 control chromosomes in the GnomAD database, including 4,948 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 0.24 (4948 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+11410C>T		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+11410C>T		intron_variant	Intron 3 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36089 AN: 151886 Hom.: 4954 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.237 AC: 36084 AN: 152004 Hom.: 4948 Cov.: 32 AF XY: 0.241 AC XY: 17917 AN XY: 74272

African (AFR) AF: 0.108 AC: 4495 AN: 41488

American (AMR) AF: 0.228 AC: 3490 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3470

East Asian (EAS) AF: 0.189 AC: 977 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1442 AN: 4804

European-Finnish (FIN) AF: 0.346 AC: 3651 AN: 10542

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20440 AN: 67952

Other (OTH) AF: 0.208 AC: 437 AN: 2106

Alfa AF: 0.269 Hom.: 15544

Bravo AF: 0.218

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.48
PhyloP100		-1.9
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: rs9555687; hg19: chr13-110971880;