rs9555703

Variant names:

• chr13-110457535-A-G
• rs9555703
• NM_001846.4:c.1432+100A>G

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.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
• Publications: 9 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 (REVEL=0.002).
• BP6: Variant 13-110457535-A-G is Benign according to our data. Variant chr13-110457535-A-G is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1432+100A>G		intron_variant	Intron 21 of 47	ENST00000360467.7	NP_001837.2
COL4A2-AS2	NR_171022.1	n.551T>C		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1432+100A>G		intron_variant	Intron 21 of 47	5	NM_001846.4	ENSP00000353654.5

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

GnomAD2 exomes AF: 0.231 AC: 37023 AN: 160604 AF XY: 0.238

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 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

African (AFR) AF: 0.141 AC: 2324 AN: 16528

American (AMR) AF: 0.145 AC: 5130 AN: 35368

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 4292 AN: 20072

East Asian (EAS) AF: 0.0878 AC: 2819 AN: 32120

South Asian (SAS) AF: 0.254 AC: 16187 AN: 63660

European-Finnish (FIN) AF: 0.234 AC: 11281 AN: 48256

Middle Eastern (MID) AF: 0.171 AC: 709 AN: 4154

European-Non Finnish (NFE) AF: 0.298 AC: 107631 AN: 361382

Other (OTH) AF: 0.237 AC: 7571 AN: 31942

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

African (AFR) AF: 0.145 AC: 6036 AN: 41544

American (AMR) AF: 0.172 AC: 2625 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3468

East Asian (EAS) AF: 0.0967 AC: 499 AN: 5158

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4830

European-Finnish (FIN) AF: 0.223 AC: 2360 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20296 AN: 67948

Other (OTH) AF: 0.209 AC: 441 AN: 2114

Alfa AF: 0.265 Hom.: 11249

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.46
PhyloP100		-0.20
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

Other links and lift over

dbSNP: rs9555703; hg19: chr13-111109882; COSMIC: COSV107471814;