NM_001846.4:c.862-41G>A

Variant names:

• chr13-110438577-G-A
• rs7984100
• NM_001846.4:c.862-41G>A

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.862-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,612,218 control chromosomes in the GnomAD database, including 73,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9846 hom., cov: 33)
  • Exomes 𝑓: 0.29 (64084 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.29
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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 (REVEL=0.002).
• BP6: Variant 13-110438577-G-A is Benign according to our data. Variant chr13-110438577-G-A is described in ClinVar as Benign. ClinVar VariationId is 1217363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.862-41G>A		intron	N/A	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.862-41G>A		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.862-41G>A		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.862-41G>A		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52318 AN: 151794 Hom.: 9838 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.282 AC: 70299 AN: 249442 AF XY: 0.280

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.289 AC: 422118 AN: 1460306 Hom.: 64084 Cov.: 33 AF XY: 0.287 AC XY: 208704 AN XY: 726538

African (AFR) AF: 0.517 AC: 17286 AN: 33454

American (AMR) AF: 0.205 AC: 9155 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11157 AN: 26122

East Asian (EAS) AF: 0.116 AC: 4604 AN: 39690

South Asian (SAS) AF: 0.224 AC: 19292 AN: 86232

European-Finnish (FIN) AF: 0.289 AC: 15408 AN: 53372

Middle Eastern (MID) AF: 0.463 AC: 2659 AN: 5746

European-Non Finnish (NFE) AF: 0.292 AC: 323853 AN: 1110628

Other (OTH) AF: 0.310 AC: 18704 AN: 60344

GnomAD4 genome AF: 0.345 AC: 52357 AN: 151912 Hom.: 9846 Cov.: 33 AF XY: 0.339 AC XY: 25192 AN XY: 74254

African (AFR) AF: 0.508 AC: 21021 AN: 41364

American (AMR) AF: 0.288 AC: 4395 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1433 AN: 3466

East Asian (EAS) AF: 0.127 AC: 657 AN: 5172

South Asian (SAS) AF: 0.207 AC: 997 AN: 4828

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10578

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19743 AN: 67916

Other (OTH) AF: 0.347 AC: 733 AN: 2114

Alfa AF: 0.285 Hom.: 1849

Bravo AF: 0.359

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Porencephaly 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.61
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7984100; hg19: chr13-111090924; COSMIC: COSV64631991;