rs16260

Positions:

• chr16-68737131-C-A

Variant summary

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

The variant allele was found at a frequency of 0.263 in 544,224 control chromosomes in the GnomAD database, including 19,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4868 hom., cov: 32)
  • Exomes 𝑓: 0.27 (14920 hom.)
• Consequence: Unknown
• Clinical Significance: Benign reviewed by expert panel B:5
• Conservation: PhyloP100: -0.0220

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 16-68737131-C-A is Benign according to our data. Variant chr16-68737131-C-A is described in ClinVar as [Benign]. Clinvar id is 12247.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr16-68737131-C-A is described in Lovd as [Pathogenic].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37459 AN: 152044 Hom.: 4870 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.270 AC: 105718 AN: 392062 Hom.: 14920 AF XY: 0.270 AC XY: 55583 AN XY: 206134

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.246 AC: 37461 AN: 152162 Hom.: 4868 Cov.: 32 AF XY: 0.246 AC XY: 18294 AN XY: 74374

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.257

Alfa AF: 0.275 Hom.: 2700

Bravo AF: 0.246

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	This variant is associated with the following publications: (PMID: 23231047, 24491043, 11896626, 10706097, 24023817, 22792244, 17960397, 21997289, 19569232, 16189707, 22194161, 18781193, 21214416, 20462505, 17201188) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary diffuse gastric adenocarcinoma Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

CDH1-related diffuse gastric and lobular breast cancer syndrome Benign:1

Benign, reviewed by expert panel

curation

ClinGen CDH1 Variant Curation Expert Panel

Aug 10, 2023

The NM_004360.4(CDH1):c.-124-161C>A variant has an allele frequency of 0.27733 (27.73%, 4262/15368 alleles, 578 homozygotes) in the European (Non-Finnish) subpopulation of the gnomAD v2.1.1 cohort (BA1; BP2). Therefore, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BP2. -

RECLASSIFIED - CDH1 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Dec 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.9
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16260; hg19: chr16-68771034;