rs391859

Variant names:

• chr13-110507957-G-A
• rs391859
• NM_001846.4:c.4617G>A
• COL4A2 p.Ala1539Ala

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001846.4(COL4A2):​c.4617G>A​(p.Ala1539Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,613,750 control chromosomes in the GnomAD database, including 7,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (795 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6523 hom.)
• Consequence: COL4A2 NM_001846.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.66
• Publications: 18 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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-110507957-G-A is Benign according to our data. Variant chr13-110507957-G-A is described in ClinVar as Benign. ClinVar VariationId is 311183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 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.4617G>A	p.Ala1539Ala	synonymous	Exon 47 of 48	NP_001837.2	P08572
	COL4A2-AS1	NR_046583.1		n.81+142C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.4617G>A	p.Ala1539Ala	synonymous	Exon 47 of 48	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.4698G>A	p.Ala1566Ala	synonymous	Exon 48 of 49	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.4617G>A	p.Ala1539Ala	synonymous	Exon 47 of 48	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14296 AN: 152048 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0625

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.106 AC: 26210 AN: 248338 AF XY: 0.101

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.0475

Gnomad NFE exome AF: 0.0872

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0876 AC: 128031 AN: 1461584 Hom.: 6523 Cov.: 31 AF XY: 0.0873 AC XY: 63503 AN XY: 727056

African (AFR) AF: 0.0787 AC: 2636 AN: 33480

American (AMR) AF: 0.204 AC: 9121 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4381 AN: 26136

East Asian (EAS) AF: 0.171 AC: 6803 AN: 39694

South Asian (SAS) AF: 0.0691 AC: 5961 AN: 86256

European-Finnish (FIN) AF: 0.0473 AC: 2518 AN: 53280

Middle Eastern (MID) AF: 0.114 AC: 656 AN: 5760

European-Non Finnish (NFE) AF: 0.0810 AC: 90087 AN: 1111872

Other (OTH) AF: 0.0972 AC: 5868 AN: 60386

GnomAD4 genome AF: 0.0941 AC: 14319 AN: 152166 Hom.: 795 Cov.: 32 AF XY: 0.0930 AC XY: 6922 AN XY: 74422

African (AFR) AF: 0.0786 AC: 3262 AN: 41520

American (AMR) AF: 0.177 AC: 2704 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 570 AN: 3464

East Asian (EAS) AF: 0.153 AC: 788 AN: 5152

South Asian (SAS) AF: 0.0621 AC: 300 AN: 4828

European-Finnish (FIN) AF: 0.0462 AC: 490 AN: 10616

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0871 AC: 5921 AN: 67980

Other (OTH) AF: 0.111 AC: 234 AN: 2112

Alfa AF: 0.0949 Hom.: 2476

Bravo AF: 0.106

Asia WGS AF: 0.103 AC: 358 AN: 3478

EpiCase AF: 0.0959

EpiControl AF: 0.0968

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Porencephaly 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.88
PhyloP100		-4.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs391859;

hg19: chr13-111160304;

COSMIC: COSV64627362;