rs7983487

Positions:

• chr13-110438507-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.862-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,399,656 control chromosomes in the GnomAD database, including 72,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11005 hom., cov: 33)
  • Exomes 𝑓: 0.31 (61534 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.372

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=-0.87).
• BP6: Variant 13-110438507-A-G is Benign according to our data. Variant chr13-110438507-A-G is described in ClinVar as [Benign]. Clinvar id is 1242395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.862-111A>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.862-111A>G		intron_variant		5	NM_001846.4	ENSP00000353654.5
COL4A2	ENST00000650540.1	c.862-111A>G		intron_variant				ENSP00000497878.1
COL4A2	ENST00000617564.2	c.118-111A>G		intron_variant		6		ENSP00000481492.3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55283 AN: 152024 Hom.: 10999 Cov.: 33

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.371

GnomAD3 exomes AF: 0.300 AC: 74190 AN: 247392 Hom.: 12430 AF XY: 0.300 AC XY: 40366 AN XY: 134344

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.306 AC: 381546 AN: 1247514 Hom.: 61534 Cov.: 18 AF XY: 0.305 AC XY: 192758 AN XY: 631810

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.466

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.364 AC: 55323 AN: 152142 Hom.: 11005 Cov.: 33 AF XY: 0.358 AC XY: 26642 AN XY: 74378

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.372

Alfa AF: 0.353 Hom.: 1929

Bravo AF: 0.375

Asia WGS AF: 0.240 AC: 836 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	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.38

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: rs7983487; hg19: chr13-111090854; COSMIC: COSV64626123;