rs3929758

Variant names:

• chr13-110429810-C-A
• rs3929758
• NM_001846.4:c.478-75C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110429810-C-A
• chr13-110429810-C-G

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.478-75C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 1,468,696 control chromosomes in the GnomAD database, including 394,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42870 hom., cov: 32)
  • Exomes 𝑓: 0.73 (352076 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.22
• Publications: 5 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 13-110429810-C-A is Benign according to our data. Variant chr13-110429810-C-A is described in ClinVar as Benign. ClinVar VariationId is 1241415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 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.478-75C>A		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.478-75C>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000619688.3	TSL:6	c.*1176C>A		3_prime_UTR	Exon 7 of 7	ENSP00000496868.2
	COL4A2	ENST00000714399.1		c.478-75C>A		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113849 AN: 151960 Hom.: 42837 Cov.: 32

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.730 AC: 961520 AN: 1316618 Hom.: 352076 AF XY: 0.730 AC XY: 482769 AN XY: 661046

African (AFR) AF: 0.811 AC: 24678 AN: 30420

American (AMR) AF: 0.661 AC: 27256 AN: 41218

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 18866 AN: 24848

East Asian (EAS) AF: 0.613 AC: 23598 AN: 38490

South Asian (SAS) AF: 0.723 AC: 58563 AN: 81008

European-Finnish (FIN) AF: 0.776 AC: 38106 AN: 49114

Middle Eastern (MID) AF: 0.772 AC: 3931 AN: 5090

European-Non Finnish (NFE) AF: 0.732 AC: 725862 AN: 991062

Other (OTH) AF: 0.734 AC: 40660 AN: 55368

GnomAD4 genome AF: 0.749 AC: 113939 AN: 152078 Hom.: 42870 Cov.: 32 AF XY: 0.751 AC XY: 55813 AN XY: 74342

African (AFR) AF: 0.808 AC: 33529 AN: 41504

American (AMR) AF: 0.720 AC: 10990 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2574 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3145 AN: 5170

South Asian (SAS) AF: 0.724 AC: 3489 AN: 4818

European-Finnish (FIN) AF: 0.786 AC: 8304 AN: 10568

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49346 AN: 67962

Other (OTH) AF: 0.744 AC: 1567 AN: 2106

Alfa AF: 0.723 Hom.: 21019

Bravo AF: 0.746

Asia WGS AF: 0.688 AC: 2394 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.045
DANN	Benign	0.38
PhyloP100		-3.2
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: rs3929758; hg19: chr13-111082157;