rs7244243

Variant names:

• chr18-65762670-C-A
• rs7244243
• NM_004361.5:c.-173C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-65762670-C-A
• chr18-65762670-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004361.5(CDH7):​c.-173C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 582,506 control chromosomes in the GnomAD database, including 36,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11541 hom., cov: 31)
  • Exomes 𝑓: 0.33 (24785 hom.)
• Consequence: CDH7 NM_004361.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 8 publications found

Genes affected

CDH7 (HGNC:1766): (cadherin 7) This gene encodes a type II 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 molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 18-65762670-C-A is Benign according to our data. Variant chr18-65762670-C-A is described in ClinVar as [Benign]. Clinvar id is 1179601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH7	NM_004361.5	c.-173C>A		5_prime_UTR_variant	Exon 2 of 12	ENST00000397968.4	NP_004352.2
CDH7	NM_001362438.2	c.-173C>A		5_prime_UTR_variant	Exon 2 of 12		NP_001349367.1
CDH7	NM_033646.4	c.-173C>A		5_prime_UTR_variant	Exon 2 of 12		NP_387450.1
CDH7	NM_001317214.3	c.-173C>A		5_prime_UTR_variant	Exon 2 of 11		NP_001304143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH7	ENST00000397968.4	c.-173C>A		5_prime_UTR_variant	Exon 2 of 12	1	NM_004361.5	ENSP00000381058.2
CDH7	ENST00000323011.7	c.-173C>A		5_prime_UTR_variant	Exon 2 of 12	1		ENSP00000319166.3
CDH7	ENST00000536984.6	c.-173C>A		5_prime_UTR_variant	Exon 2 of 11	1		ENSP00000443030.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57252 AN: 151646 Hom.: 11520 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.331 AC: 142390 AN: 430742 Hom.: 24785 Cov.: 4 AF XY: 0.335 AC XY: 75922 AN XY: 226420

African (AFR) AF: 0.524 AC: 6307 AN: 12044

American (AMR) AF: 0.287 AC: 5217 AN: 18158

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 3660 AN: 13072

East Asian (EAS) AF: 0.347 AC: 10519 AN: 30292

South Asian (SAS) AF: 0.427 AC: 17331 AN: 40608

European-Finnish (FIN) AF: 0.387 AC: 10933 AN: 28236

Middle Eastern (MID) AF: 0.406 AC: 760 AN: 1870

European-Non Finnish (NFE) AF: 0.303 AC: 79124 AN: 261378

Other (OTH) AF: 0.340 AC: 8539 AN: 25084

GnomAD4 genome AF: 0.378 AC: 57307 AN: 151764 Hom.: 11541 Cov.: 31 AF XY: 0.382 AC XY: 28336 AN XY: 74158

African (AFR) AF: 0.520 AC: 21525 AN: 41372

American (AMR) AF: 0.298 AC: 4537 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3470

East Asian (EAS) AF: 0.345 AC: 1774 AN: 5136

South Asian (SAS) AF: 0.443 AC: 2124 AN: 4796

European-Finnish (FIN) AF: 0.413 AC: 4339 AN: 10516

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20809 AN: 67930

Other (OTH) AF: 0.340 AC: 717 AN: 2106

Alfa AF: 0.313 Hom.: 7617

Bravo AF: 0.370

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 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	-0.40
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		1.3
Mutation Taster		=295/5	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: rs7244243; hg19: chr18-63429906;