13-110424593-T-C

Variant names:

• chr13-110424593-T-C
• rs4771678
• NM_001846.4:c.181-141T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.181-141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 514,626 control chromosomes in the GnomAD database, including 135,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (37368 hom., cov: 25)
  • Exomes 𝑓: 0.73 (98300 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-110424593-T-C is Benign according to our data. Variant chr13-110424593-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.181-141T>C		intron	N/A	NP_001837.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.181-141T>C		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.181-141T>C		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.181-141T>C		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.705 AC: 105542 AN: 149790 Hom.: 37348 Cov.: 25

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.731 AC: 266451 AN: 364726 Hom.: 98300 AF XY: 0.731 AC XY: 137858 AN XY: 188526

African (AFR) AF: 0.668 AC: 7571 AN: 11340

American (AMR) AF: 0.797 AC: 10118 AN: 12688

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 7721 AN: 11396

East Asian (EAS) AF: 0.827 AC: 24347 AN: 29448

South Asian (SAS) AF: 0.743 AC: 14642 AN: 19698

European-Finnish (FIN) AF: 0.748 AC: 23356 AN: 31228

Middle Eastern (MID) AF: 0.622 AC: 1006 AN: 1618

European-Non Finnish (NFE) AF: 0.719 AC: 162179 AN: 225646

Other (OTH) AF: 0.716 AC: 15511 AN: 21664

GnomAD4 genome AF: 0.705 AC: 105609 AN: 149900 Hom.: 37368 Cov.: 25 AF XY: 0.705 AC XY: 51539 AN XY: 73070

African (AFR) AF: 0.665 AC: 27021 AN: 40638

American (AMR) AF: 0.753 AC: 11358 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2338 AN: 3460

East Asian (EAS) AF: 0.824 AC: 4172 AN: 5064

South Asian (SAS) AF: 0.708 AC: 3340 AN: 4716

European-Finnish (FIN) AF: 0.723 AC: 7323 AN: 10126

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 47799 AN: 67548

Other (OTH) AF: 0.686 AC: 1426 AN: 2080

Alfa AF: 0.705 Hom.: 20588

Bravo AF: 0.705

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0030
DANN	Benign	0.47
PhyloP100		-0.66
PromoterAI		-0.013	Neutral
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: rs4771678; hg19: chr13-111076940;