rs13072748

Variant names:

• chr3-49799799-C-T
• rs13072748
• NM_001007540.4:c.14G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007540.4(CDHR4):​c.14G>A​(p.Arg5Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDHR4 NM_001007540.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

CDHR4 (HGNC:34527): (cadherin related family member 4) Predicted to enable calcium ion binding activity. Predicted to be involved in cell adhesion. Predicted to be located in membrane. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072621435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR4	NM_001007540.4	c.14G>A	p.Arg5Lys	missense_variant	Exon 1 of 19	ENST00000412678.7	NP_001007541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR4	ENST00000412678.7	c.14G>A	p.Arg5Lys	missense_variant	Exon 1 of 19	1	NM_001007540.4	ENSP00000391409.2
CDHR4	ENST00000343366.8	c.14G>A	p.Arg5Lys	missense_variant	Exon 1 of 3	1		ENSP00000341302.4
CDHR4	ENST00000487256.1	c.14G>A	p.Arg5Lys	missense_variant	Exon 1 of 4	5		ENSP00000420677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.0074	T;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.35	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.69	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.37	T;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.17
MutPred		0.41		Gain of ubiquitination at R5 (P = 0.0162);Gain of ubiquitination at R5 (P = 0.0162);Gain of ubiquitination at R5 (P = 0.0162);
MVP		0.26
MPC		0.079
ClinPred		0.12	T
GERP RS		2.8
Varity_R		0.047
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13072748; hg19: chr3-49837232;