7-105981070-G-A

Variant names:

• chr7-105981070-G-A
• rs368251641
• NM_152750.5:c.352G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152750.5(CDHR3):​c.352G>A​(p.Val118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.351
• Publications: 0 publications found

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307029 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02049005).
• BP6: Variant 7-105981070-G-A is Benign according to our data. Variant chr7-105981070-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3265369.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR3	NM_152750.5	c.352G>A	p.Val118Ile	missense_variant	Exon 3 of 19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2	c.88G>A	p.Val30Ile	missense_variant	Exon 2 of 18		NP_001288090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14	c.352G>A	p.Val118Ile	missense_variant	Exon 3 of 19	1	NM_152750.5	ENSP00000325954.9

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152236 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 248172 AF XY: 0.00

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461252 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726838

African (AFR) AF: 0.000179 AC: 6 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111704

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152236 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

African (AFR) AF: 0.000193 AC: 8 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.000250 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 30, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.075
DANN	Benign	0.47
DEOGEN2	Benign	0.00047	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;.
PhyloP100		-0.35
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.038
Sift	Benign	0.68	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.035
MVP		0.088
MPC		0.031
ClinPred		0.0092	T
GERP RS		-10
Varity_R		0.11
gMVP		0.077
Mutation Taster		=79/21	polymorphism

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: rs368251641; hg19: chr7-105621516;