chr13-110397276-T-C

Variant names:

• chr13-110397276-T-C
• rs9515203
• NM_001846.4:c.181-27458T>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.181-27458T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,192 control chromosomes in the GnomAD database, including 5,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5336 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 58 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.87).
• BP6: Variant 13-110397276-T-C is Benign according to our data. Variant chr13-110397276-T-C is described in ClinVar as Benign. ClinVar VariationId is 1164920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.29 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.181-27458T>C		intron	N/A	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.181-27458T>C		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.181-27458T>C		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.181-27458T>C		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39286 AN: 152074 Hom.: 5337 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.258 AC: 39295 AN: 152192 Hom.: 5336 Cov.: 33 AF XY: 0.256 AC XY: 19036 AN XY: 74394

African (AFR) AF: 0.270 AC: 11223 AN: 41520

American (AMR) AF: 0.297 AC: 4540 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3470

East Asian (EAS) AF: 0.120 AC: 623 AN: 5188

South Asian (SAS) AF: 0.160 AC: 774 AN: 4828

European-Finnish (FIN) AF: 0.256 AC: 2707 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17729 AN: 68000

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.255 Hom.: 14094

Bravo AF: 0.266

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

ClinVar submissions

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	-0.87
CADD	Benign	0.98
DANN	Benign	0.27
PhyloP100		-1.4
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: rs9515203; hg19: chr13-111049623;