chr13-110506527-A-G

Variant names:

• chr13-110506527-A-G
• rs445348
• NM_001846.4:c.4515A>G

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.4515A>G​(p.Pro1505Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,612,360 control chromosomes in the GnomAD database, including 615,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54015 hom., cov: 33)
  • Exomes 𝑓: 0.87 (561287 hom.)
• Consequence: COL4A2 NM_001846.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -9.52
• Publications: 29 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=-0.86).
• BP6: Variant 13-110506527-A-G is Benign according to our data. Variant chr13-110506527-A-G is described in ClinVar as Benign. ClinVar VariationId is 311180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 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.4515A>G	p.Pro1505Pro	synonymous	Exon 46 of 48	NP_001837.2	P08572
	COL4A2-AS1	NR_046583.1		n.186+1120T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.4515A>G	p.Pro1505Pro	synonymous	Exon 46 of 48	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.4596A>G	p.Pro1532Pro	synonymous	Exon 47 of 49	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.4515A>G	p.Pro1505Pro	synonymous	Exon 46 of 48	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127688 AN: 152070 Hom.: 54013 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.861

GnomAD2 exomes AF: 0.829 AC: 202816 AN: 244712 AF XY: 0.834

Gnomad AFR exome AF: 0.782

Gnomad AMR exome AF: 0.769

Gnomad ASJ exome AF: 0.888

Gnomad EAS exome AF: 0.576

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.860

GnomAD4 exome AF: 0.874 AC: 1276210 AN: 1460172 Hom.: 561287 Cov.: 66 AF XY: 0.873 AC XY: 633832 AN XY: 726328

African (AFR) AF: 0.780 AC: 26121 AN: 33470

American (AMR) AF: 0.776 AC: 34437 AN: 44360

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 23186 AN: 26082

East Asian (EAS) AF: 0.570 AC: 22574 AN: 39630

South Asian (SAS) AF: 0.787 AC: 67665 AN: 85980

European-Finnish (FIN) AF: 0.816 AC: 43237 AN: 53018

Middle Eastern (MID) AF: 0.917 AC: 5288 AN: 5764

European-Non Finnish (NFE) AF: 0.901 AC: 1001932 AN: 1111544

Other (OTH) AF: 0.858 AC: 51770 AN: 60324

GnomAD4 genome AF: 0.839 AC: 127740 AN: 152188 Hom.: 54015 Cov.: 33 AF XY: 0.833 AC XY: 62011 AN XY: 74406

African (AFR) AF: 0.781 AC: 32432 AN: 41500

American (AMR) AF: 0.836 AC: 12796 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3044 AN: 3472

East Asian (EAS) AF: 0.577 AC: 2973 AN: 5152

South Asian (SAS) AF: 0.770 AC: 3715 AN: 4826

European-Finnish (FIN) AF: 0.807 AC: 8557 AN: 10608

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61314 AN: 68012

Other (OTH) AF: 0.856 AC: 1808 AN: 2112

Alfa AF: 0.882 Hom.: 127300

Bravo AF: 0.838

Asia WGS AF: 0.700 AC: 2438 AN: 3478

EpiCase AF: 0.907

EpiControl AF: 0.908

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-9.5
PromoterAI		-0.038	Neutral
Mutation Taster		=99/1	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: rs445348; hg19: chr13-111158874; COSMIC: COSV100847257; COSMIC: COSV100847257;