chr13-110401612-G-T

Variant names:

• chr13-110401612-G-T
• rs1927343
• NM_001846.4:c.181-23122G>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.181-23122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,118 control chromosomes in the GnomAD database, including 26,969 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 0.59 (26969 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.657 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.181-23122G>T		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.181-23122G>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.181-23122G>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.181-23122G>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89529 AN: 152000 Hom.: 26969 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.589 AC: 89565 AN: 152118 Hom.: 26969 Cov.: 33 AF XY: 0.585 AC XY: 43486 AN XY: 74358

African (AFR) AF: 0.460 AC: 19105 AN: 41488

American (AMR) AF: 0.653 AC: 9988 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1979 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2556 AN: 5172

South Asian (SAS) AF: 0.551 AC: 2658 AN: 4826

European-Finnish (FIN) AF: 0.594 AC: 6271 AN: 10556

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45019 AN: 67996

Other (OTH) AF: 0.567 AC: 1196 AN: 2108

Alfa AF: 0.626 Hom.: 15416

Bravo AF: 0.589

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.028
DANN	Benign	0.51
PhyloP100		-4.0
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: rs1927343; hg19: chr13-111053959;