13-110491408-T-C

Variant names:

• chr13-110491408-T-C
• rs413756
• NM_001846.4:c.3454+68T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.3454+68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,033,438 control chromosomes in the GnomAD database, including 260,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37755 hom., cov: 31)
  • Exomes 𝑓: 0.71 (222719 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.166
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110491408-T-C is Benign according to our data. Variant chr13-110491408-T-C is described in ClinVar as [Benign]. Clinvar id is 1246617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3454+68T>C		intron_variant	Intron 37 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3454+68T>C		intron_variant	Intron 37 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106995 AN: 151896 Hom.: 37718 Cov.: 31

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.709 AC: 624987 AN: 881424 Hom.: 222719 AF XY: 0.710 AC XY: 322324 AN XY: 454092

African (AFR) AF: 0.715 AC: 15444 AN: 21602

American (AMR) AF: 0.668 AC: 23253 AN: 34802

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 14829 AN: 21876

East Asian (EAS) AF: 0.791 AC: 26369 AN: 33340

South Asian (SAS) AF: 0.729 AC: 50217 AN: 68922

European-Finnish (FIN) AF: 0.749 AC: 35919 AN: 47934

Middle Eastern (MID) AF: 0.748 AC: 3502 AN: 4680

European-Non Finnish (NFE) AF: 0.703 AC: 426782 AN: 607384

Other (OTH) AF: 0.701 AC: 28672 AN: 40884

GnomAD4 genome AF: 0.704 AC: 107083 AN: 152014 Hom.: 37755 Cov.: 31 AF XY: 0.708 AC XY: 52621 AN XY: 74286

African (AFR) AF: 0.705 AC: 29229 AN: 41440

American (AMR) AF: 0.665 AC: 10162 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2342 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4054 AN: 5156

South Asian (SAS) AF: 0.739 AC: 3565 AN: 4822

European-Finnish (FIN) AF: 0.747 AC: 7899 AN: 10568

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47486 AN: 67972

Other (OTH) AF: 0.693 AC: 1463 AN: 2110

Alfa AF: 0.700 Hom.: 40878

Bravo AF: 0.697

Asia WGS AF: 0.765 AC: 2660 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.29
PhyloP100		0.17
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: rs413756; hg19: chr13-111143755;