rs7992330

Variant names:

• chr13-110462404-G-A
• rs7992330
• NM_001846.4:c.1776+20G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110462404-G-A
• chr13-110462404-G-T

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.1776+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,609,344 control chromosomes in the GnomAD database, including 62,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4444 hom., cov: 33)
  • Exomes 𝑓: 0.28 (58437 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.302
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-110462404-G-A is Benign according to our data. Variant chr13-110462404-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 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.1776+20G>A		intron	N/A	NP_001837.2
	COL4A2-AS2	NR_171022.1		n.265+619C>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.1776+20G>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000478681.1	TSL:3	n.292G>A		non_coding_transcript_exon	Exon 2 of 2
	COL4A2	ENST00000714399.1		c.1857+20G>A		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34659 AN: 152090 Hom.: 4444 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.231 AC: 56185 AN: 242810 AF XY: 0.238

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.0880

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.293

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.277 AC: 403539 AN: 1457136 Hom.: 58437 Cov.: 32 AF XY: 0.277 AC XY: 200672 AN XY: 724980

African (AFR) AF: 0.140 AC: 4666 AN: 33436

American (AMR) AF: 0.145 AC: 6472 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5507 AN: 26114

East Asian (EAS) AF: 0.0878 AC: 3484 AN: 39680

South Asian (SAS) AF: 0.251 AC: 21610 AN: 86136

European-Finnish (FIN) AF: 0.235 AC: 12000 AN: 51160

Middle Eastern (MID) AF: 0.166 AC: 845 AN: 5096

European-Non Finnish (NFE) AF: 0.301 AC: 333814 AN: 1110622

Other (OTH) AF: 0.251 AC: 15141 AN: 60216

GnomAD4 genome AF: 0.228 AC: 34661 AN: 152208 Hom.: 4444 Cov.: 33 AF XY: 0.224 AC XY: 16651 AN XY: 74426

African (AFR) AF: 0.145 AC: 6040 AN: 41536

American (AMR) AF: 0.173 AC: 2639 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3472

East Asian (EAS) AF: 0.0964 AC: 499 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1160 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2362 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20300 AN: 67992

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.261 Hom.: 1064

Bravo AF: 0.215

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.71
PhyloP100		0.30
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: rs7992330; hg19: chr13-111114751; COSMIC: COSV64636707; COSMIC: COSV64636707;