rs4773194

Variant names:

• chr13-110480143-A-G
• rs4773194
• NM_001846.4:c.2588-77A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-110480143-A-G
• chr13-110480143-A-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.2588-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,423,328 control chromosomes in the GnomAD database, including 476,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50726 hom., cov: 34)
  • Exomes 𝑓: 0.82 (425950 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.257
• 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=-0.99).
• BP6: Variant 13-110480143-A-G is Benign according to our data. Variant chr13-110480143-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2588-77A>G		intron_variant	Intron 30 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2588-77A>G		intron_variant	Intron 30 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124095 AN: 152134 Hom.: 50674 Cov.: 34

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.834

GnomAD4 exome AF: 0.818 AC: 1039608 AN: 1271076 Hom.: 425950 AF XY: 0.820 AC XY: 514424 AN XY: 627224

African (AFR) AF: 0.778 AC: 21968 AN: 28228

American (AMR) AF: 0.870 AC: 24665 AN: 28340

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 16796 AN: 19294

East Asian (EAS) AF: 0.875 AC: 32306 AN: 36936

South Asian (SAS) AF: 0.871 AC: 56723 AN: 65112

European-Finnish (FIN) AF: 0.847 AC: 41665 AN: 49180

Middle Eastern (MID) AF: 0.887 AC: 3148 AN: 3548

European-Non Finnish (NFE) AF: 0.809 AC: 798783 AN: 987734

Other (OTH) AF: 0.826 AC: 43554 AN: 52704

GnomAD4 genome AF: 0.816 AC: 124208 AN: 152252 Hom.: 50726 Cov.: 34 AF XY: 0.818 AC XY: 60919 AN XY: 74448

African (AFR) AF: 0.785 AC: 32583 AN: 41526

American (AMR) AF: 0.854 AC: 13070 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2975 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4340 AN: 5178

South Asian (SAS) AF: 0.870 AC: 4196 AN: 4824

European-Finnish (FIN) AF: 0.854 AC: 9064 AN: 10616

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55334 AN: 68016

Other (OTH) AF: 0.837 AC: 1767 AN: 2112

Alfa AF: 0.817 Hom.: 31104

Bravo AF: 0.811

Asia WGS AF: 0.861 AC: 2996 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

- -

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	-0.99
CADD	Benign	0.23
DANN	Benign	0.40
PhyloP100		-0.26
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: rs4773194; hg19: chr13-111132490; COSMIC: COSV64626218;