rs200892741

Variant names:

• chr7-105981016-A-G
• rs200892741
• NM_152750.5:c.298A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152750.5(CDHR3):​c.298A>G​(p.Ile100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,611,542 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• 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]

ENSG00000307029 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.013440013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR3	NM_152750.5	c.298A>G	p.Ile100Val	missense_variant	Exon 3 of 19	ENST00000317716.14	NP_689963.2
CDHR3	NM_001301161.2	c.34A>G	p.Ile12Val	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.298A>G	p.Ile100Val	missense_variant	Exon 3 of 19	1	NM_152750.5	ENSP00000325954.9

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152236 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000956

GnomAD2 exomes AF: 0.0000818 AC: 20 AN: 244594 AF XY: 0.0000831

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1459188 Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15 AN XY: 725486

African (AFR) AF: 0.000717 AC: 24 AN: 33464

American (AMR) AF: 0.0000901 AC: 4 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 85488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110770

Other (OTH) AF: 0.000116 AC: 7 AN: 60298

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152354 Hom.: 0 Cov.: 30 AF XY: 0.000174 AC XY: 13 AN XY: 74504

African (AFR) AF: 0.000722 AC: 30 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.000276

ESP6500AA AF: 0.000781 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000910 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298A>G (p.I100V) alteration is located in exon 3 (coding exon 3) of the CDHR3 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the isoleucine (I) at amino acid position 100 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.029
DANN	Benign	0.36
DEOGEN2	Benign	0.00053	T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.013	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.98	L;.
PhyloP100		-1.2
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.033
MVP		0.18
MPC		0.031
ClinPred		0.0042	T
GERP RS		-0.42
Varity_R		0.077
gMVP		0.095
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200892741; hg19: chr7-105621462;