7-105984273-G-A

Variant names:

• chr7-105984273-G-A
• rs144538079
• NM_152750.5:c.497G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_152750.5(CDHR3):​c.497G>A​(p.Arg166Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,609,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 7-105984273-G-A is Benign according to our data. Variant chr7-105984273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3999134.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.497G>A	p.Arg166Gln	missense_variant	Exon 4 of 19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2	c.233G>A	p.Arg78Gln	missense_variant	Exon 3 of 18		NP_001288090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR3	ENST00000317716.14	c.497G>A	p.Arg166Gln	missense_variant	Exon 4 of 19	1	NM_152750.5	ENSP00000325954.9

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000526 AC: 13 AN: 247180 AF XY: 0.0000447

Gnomad AFR exome AF: 0.000328

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000559

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000445

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1457478 Hom.: 0 Cov.: 30 AF XY: 0.0000304 AC XY: 22 AN XY: 724766

African (AFR) AF: 0.000239 AC: 8 AN: 33406

American (AMR) AF: 0.0000224 AC: 1 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85416

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53312

Middle Eastern (MID) AF: 0.000870 AC: 5 AN: 5748

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1109194

Other (OTH) AF: 0.0000498 AC: 3 AN: 60206

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74468

African (AFR) AF: 0.000529 AC: 22 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0209 Hom.: 2321

Bravo AF: 0.000178

ESP6500AA AF: 0.000518 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000414 AC: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 06, 2025

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	0.065
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.25
DANN	Benign	0.58
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	N;.
PhyloP100		-1.8
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.014
Sift	Benign	0.68	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	B;.
Vest4		0.17
MVP		0.072
MPC		0.038
ClinPred		0.0063	T
GERP RS		-3.7
Varity_R		0.020
gMVP		0.092
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.23		Position offset: 16

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

Other links and lift over

dbSNP: rs144538079; hg19: chr7-105624719; COSMIC: COSV58416407;