chr13-110308338-T-C

Variant names:

• chr13-110308338-T-C
• rs4773143
• NM_001846.4:c.99+215T>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.99+215T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,948 control chromosomes in the GnomAD database, including 13,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (13764 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00100
• Publications: 15 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 13-110308338-T-C is Benign according to our data. Variant chr13-110308338-T-C is described in ClinVar as Benign. ClinVar VariationId is 1224954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.99+215T>C		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+215T>C		intron_variant	Intron 3 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64401 AN: 151830 Hom.: 13740 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.424 AC: 64469 AN: 151948 Hom.: 13764 Cov.: 32 AF XY: 0.423 AC XY: 31417 AN XY: 74254

African (AFR) AF: 0.404 AC: 16721 AN: 41430

American (AMR) AF: 0.450 AC: 6880 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2005 AN: 5138

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4810

European-Finnish (FIN) AF: 0.407 AC: 4297 AN: 10556

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29490 AN: 67938

Other (OTH) AF: 0.463 AC: 975 AN: 2108

Alfa AF: 0.418 Hom.: 3294

Bravo AF: 0.425

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.8
DANN	Benign	0.32
PhyloP100		-0.0010
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: rs4773143; hg19: chr13-110960685;