rs3803229

Positions:

• chr13-110482433-G-A

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.2759-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,463,490 control chromosomes in the GnomAD database, including 75,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6638 hom., cov: 34)
  • Exomes 𝑓: 0.32 (69290 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.127

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-110482433-G-A is Benign according to our data. Variant chr13-110482433-G-A is described in ClinVar as [Benign]. Clinvar id is 1261857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2759-83G>A		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2759-83G>A		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2	ENST00000483683.2	n.389-83G>A		intron_variant, non_coding_transcript_variant		2
COL4A2	ENST00000650225.1	n.414-83G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42694 AN: 152094 Hom.: 6631 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.323 AC: 422961 AN: 1311278 Hom.: 69290 AF XY: 0.323 AC XY: 210354 AN XY: 652108

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.307

GnomAD4 genome AF: 0.281 AC: 42711 AN: 152212 Hom.: 6638 Cov.: 34 AF XY: 0.288 AC XY: 21402 AN XY: 74416

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.284

Alfa AF: 0.306 Hom.: 9424

Bravo AF: 0.270

Asia WGS AF: 0.320 AC: 1112 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	-0.92
CADD	Benign	1.9
DANN	Benign	0.73

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: rs3803229; hg19: chr13-111134780; COSMIC: COSV64626249;