rs3803237

Variant names:

• chr13-110465321-G-A
• rs3803237
• NM_001846.4:c.1777-84G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110465321-G-A
• chr13-110465321-G-C
• chr13-110465321-G-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.1777-84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,481,516 control chromosomes in the GnomAD database, including 26,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2964 hom., cov: 34)
  • Exomes 𝑓: 0.18 (23777 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.546
• Publications: 8 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=-0.93).
• BP6: Variant 13-110465321-G-A is Benign according to our data. Variant chr13-110465321-G-A is described in ClinVar as Benign. ClinVar VariationId is 1272038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1777-84G>A		intron_variant	Intron 24 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1777-84G>A		intron_variant	Intron 24 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28824 AN: 152064 Hom.: 2964 Cov.: 34

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.183 AC: 243648 AN: 1329334 Hom.: 23777 AF XY: 0.182 AC XY: 118867 AN XY: 654004

African (AFR) AF: 0.225 AC: 6541 AN: 29106

American (AMR) AF: 0.129 AC: 3821 AN: 29586

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 5310 AN: 19990

East Asian (EAS) AF: 0.0139 AC: 531 AN: 38318

South Asian (SAS) AF: 0.107 AC: 7276 AN: 68220

European-Finnish (FIN) AF: 0.147 AC: 7128 AN: 48380

Middle Eastern (MID) AF: 0.293 AC: 1063 AN: 3630

European-Non Finnish (NFE) AF: 0.194 AC: 201684 AN: 1037210

Other (OTH) AF: 0.188 AC: 10294 AN: 54894

GnomAD4 genome AF: 0.190 AC: 28846 AN: 152182 Hom.: 2964 Cov.: 34 AF XY: 0.184 AC XY: 13708 AN XY: 74406

African (AFR) AF: 0.223 AC: 9238 AN: 41500

American (AMR) AF: 0.181 AC: 2771 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3472

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5184

South Asian (SAS) AF: 0.104 AC: 501 AN: 4810

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10598

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13027 AN: 68006

Other (OTH) AF: 0.215 AC: 453 AN: 2110

Alfa AF: 0.197 Hom.: 9921

Bravo AF: 0.195

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		-0.55
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: rs3803237; hg19: chr13-111117668;