13-110465637-C-T

Variant names:

• chr13-110465637-C-T
• rs3825490
• NM_001846.4:c.1978+31C>T

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.1978+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,552,914 control chromosomes in the GnomAD database, including 6,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (660 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5924 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.285
• Publications: 7 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=-0.88).
• BP6: Variant 13-110465637-C-T is Benign according to our data. Variant chr13-110465637-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 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.1978+31C>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.1978+31C>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.2059+31C>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.1978+31C>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11365 AN: 152204 Hom.: 652 Cov.: 33

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0865

GnomAD2 exomes AF: 0.103 AC: 22112 AN: 215038 AF XY: 0.0950

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.0696

Gnomad NFE exome AF: 0.0735

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0785 AC: 109982 AN: 1400592 Hom.: 5924 Cov.: 24 AF XY: 0.0770 AC XY: 53803 AN XY: 698426

African (AFR) AF: 0.0207 AC: 649 AN: 31376

American (AMR) AF: 0.239 AC: 9188 AN: 38428

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2834 AN: 24276

East Asian (EAS) AF: 0.259 AC: 10147 AN: 39234

South Asian (SAS) AF: 0.0414 AC: 3391 AN: 81854

European-Finnish (FIN) AF: 0.0693 AC: 3602 AN: 51984

Middle Eastern (MID) AF: 0.0750 AC: 362 AN: 4826

European-Non Finnish (NFE) AF: 0.0702 AC: 75161 AN: 1070678

Other (OTH) AF: 0.0802 AC: 4648 AN: 57936

GnomAD4 genome AF: 0.0747 AC: 11385 AN: 152322 Hom.: 660 Cov.: 33 AF XY: 0.0753 AC XY: 5609 AN XY: 74474

African (AFR) AF: 0.0256 AC: 1063 AN: 41586

American (AMR) AF: 0.168 AC: 2577 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1170 AN: 5172

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4826

European-Finnish (FIN) AF: 0.0726 AC: 771 AN: 10614

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4876 AN: 68030

Other (OTH) AF: 0.0870 AC: 184 AN: 2114

Alfa AF: 0.0787 Hom.: 1094

Bravo AF: 0.0835

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.28
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: rs3825490; hg19: chr13-111117984; COSMIC: COSV64630132; COSMIC: COSV64630132;