rs9555703

Positions:

• chr13-110457535-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.1432+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 765,636 control chromosomes in the GnomAD database, including 26,324 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: 0.26 (21880 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.198

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-110457535-A-G is Benign according to our data. Variant chr13-110457535-A-G is described in ClinVar as [Benign]. Clinvar id is 1271299.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1432+100A>G		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.551T>C		non_coding_transcript_exon_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1432+100A>G		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2-AS2	ENST00000458403.2	n.551T>C		non_coding_transcript_exon_variant	4/5	2
COL4A2	ENST00000617564.2	c.689+100A>G		intron_variant				ENSP00000481492

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34652 AN: 152036 Hom.: 4444 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.231 AC: 37023 AN: 160604 Hom.: 4747 AF XY: 0.238 AC XY: 20369 AN XY: 85716

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0903

Gnomad SAS exome AF: 0.256

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.257 AC: 157944 AN: 613482 Hom.: 21880 Cov.: 7 AF XY: 0.260 AC XY: 85470 AN XY: 329008

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0878

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.228 AC: 34653 AN: 152154 Hom.: 4444 Cov.: 33 AF XY: 0.224 AC XY: 16653 AN XY: 74382

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.209

Alfa AF: 0.256 Hom.: 3927

Bravo AF: 0.215

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs9555703; hg19: chr13-111109882;