rs16958383

Variant names:

• chr16-68823097-G-A
• rs16958383
• NM_004360.5:c.1937-302G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004360.5(CDH1):​c.1937-302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 364,374 control chromosomes in the GnomAD database, including 5,473 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2980 hom., cov: 30)
  • Exomes 𝑓: 0.14 (2493 hom.)
• Consequence: CDH1 NM_004360.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• Publications: 13 publications found

Genes affected

CDH1 (HGNC:1748): (cadherin 1) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16. [provided by RefSeq, Nov 2015]

FTLP14 (HGNC:37964): (ferritin light chain pseudogene 14)

ENSG00000260798 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-68823097-G-A is Benign according to our data. Variant chr16-68823097-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH1	NM_004360.5	MANE Select	c.1937-302G>A		intron	N/A	NP_004351.1	A0A0U2ZQU7
	CDH1	NM_001317184.2		c.1754-302G>A		intron	N/A	NP_001304113.1	P12830-2
	CDH1	NM_001317185.2		c.389-302G>A		intron	N/A	NP_001304114.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH1	ENST00000261769.10	TSL:1 MANE Select	c.1937-302G>A		intron	N/A	ENSP00000261769.4	P12830-1
	CDH1	ENST00000422392.6	TSL:1	c.1754-302G>A		intron	N/A	ENSP00000414946.2	P12830-2
	CDH1	ENST00000562836.5	TSL:1	n.2008-302G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28336 AN: 151728 Hom.: 2972 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.144 AC: 30686 AN: 212524 Hom.: 2493 Cov.: 0 AF XY: 0.139 AC XY: 15769 AN XY: 113688

African (AFR) AF: 0.286 AC: 1661 AN: 5816

American (AMR) AF: 0.120 AC: 989 AN: 8210

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 900 AN: 6356

East Asian (EAS) AF: 0.176 AC: 2035 AN: 11572

South Asian (SAS) AF: 0.0795 AC: 2207 AN: 27764

European-Finnish (FIN) AF: 0.162 AC: 1457 AN: 8994

Middle Eastern (MID) AF: 0.111 AC: 99 AN: 894

European-Non Finnish (NFE) AF: 0.149 AC: 19522 AN: 131096

Other (OTH) AF: 0.154 AC: 1816 AN: 11822

GnomAD4 genome AF: 0.187 AC: 28362 AN: 151850 Hom.: 2980 Cov.: 30 AF XY: 0.182 AC XY: 13531 AN XY: 74242

African (AFR) AF: 0.290 AC: 12022 AN: 41402

American (AMR) AF: 0.129 AC: 1965 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1004 AN: 5152

South Asian (SAS) AF: 0.0802 AC: 385 AN: 4802

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10554

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10348 AN: 67892

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.162 Hom.: 8054

Bravo AF: 0.193

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.58
PhyloP100		-1.7
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: rs16958383; hg19: chr16-68857000;