rs7990214

Variant names:

• chr13-110458826-G-A
• rs7990214
• NM_001846.4:c.1488G>A

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.1488G>A​(p.Pro496Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,380 control chromosomes in the GnomAD database, including 273,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25717 hom., cov: 31)
  • Exomes 𝑓: 0.58 (248200 hom.)
• Consequence: COL4A2 NM_001846.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.28
• Publications: 24 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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-110458826-G-A is Benign according to our data. Variant chr13-110458826-G-A is described in ClinVar as Benign. ClinVar VariationId is 311128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 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.1488G>A	p.Pro496Pro	synonymous	Exon 22 of 48	NP_001837.2
	COL4A2-AS2	NR_171022.1		n.266-540C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.1488G>A	p.Pro496Pro	synonymous	Exon 22 of 48	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.1569G>A	p.Pro523Pro	synonymous	Exon 23 of 49	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.1488G>A	p.Pro496Pro	synonymous	Exon 22 of 48	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86933 AN: 151882 Hom.: 25692 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.579

GnomAD2 exomes AF: 0.521 AC: 129568 AN: 248926 AF XY: 0.525

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.386

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.575 AC: 840890 AN: 1461380 Hom.: 248200 Cov.: 55 AF XY: 0.574 AC XY: 416948 AN XY: 726986

African (AFR) AF: 0.644 AC: 21540 AN: 33446

American (AMR) AF: 0.395 AC: 17639 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17358 AN: 26104

East Asian (EAS) AF: 0.184 AC: 7316 AN: 39664

South Asian (SAS) AF: 0.479 AC: 41306 AN: 86234

European-Finnish (FIN) AF: 0.446 AC: 23780 AN: 53372

Middle Eastern (MID) AF: 0.673 AC: 3879 AN: 5762

European-Non Finnish (NFE) AF: 0.606 AC: 673348 AN: 1111754

Other (OTH) AF: 0.575 AC: 34724 AN: 60372

GnomAD4 genome AF: 0.572 AC: 87008 AN: 152000 Hom.: 25717 Cov.: 31 AF XY: 0.560 AC XY: 41594 AN XY: 74296

African (AFR) AF: 0.634 AC: 26245 AN: 41408

American (AMR) AF: 0.489 AC: 7476 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5156

South Asian (SAS) AF: 0.459 AC: 2205 AN: 4808

European-Finnish (FIN) AF: 0.429 AC: 4544 AN: 10584

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40977 AN: 67990

Other (OTH) AF: 0.578 AC: 1216 AN: 2102

Alfa AF: 0.599 Hom.: 21169

Bravo AF: 0.579

Asia WGS AF: 0.372 AC: 1296 AN: 3478

EpiCase AF: 0.607

EpiControl AF: 0.609

ClinVar

ClinVar submissions as Germline

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	-0.78
CADD	Benign	0.095
DANN	Benign	0.83
PhyloP100		-2.3
Mutation Taster		=98/2	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: rs7990214; hg19: chr13-111111173; COSMIC: COSV64626282; COSMIC: COSV64626282;