rs1927349

Variant names:

• chr13-110406782-C-T
• rs1927349
• NM_001846.4:c.181-17952C>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.181-17952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,082 control chromosomes in the GnomAD database, including 28,592 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 0.61 (28592 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.181-17952C>T		intron_variant	Intron 4 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.181-17952C>T		intron_variant	Intron 4 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92793 AN: 151964 Hom.: 28588 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.610 AC: 92839 AN: 152082 Hom.: 28592 Cov.: 33 AF XY: 0.606 AC XY: 45043 AN XY: 74324

African (AFR) AF: 0.536 AC: 22205 AN: 41462

American (AMR) AF: 0.662 AC: 10118 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2571 AN: 5180

South Asian (SAS) AF: 0.553 AC: 2663 AN: 4818

European-Finnish (FIN) AF: 0.594 AC: 6260 AN: 10546

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45017 AN: 68000

Other (OTH) AF: 0.582 AC: 1229 AN: 2110

Alfa AF: 0.634 Hom.: 3841

Bravo AF: 0.615

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.094
DANN	Benign	0.61
PhyloP100		-1.8
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: rs1927349; hg19: chr13-111059129;