Genetic Variant CHERP:p.Arg770His (chr19-16520400-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006387.6(CHERP):c.2309G>A(p.Arg770His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CHERP
NM_006387.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.62

Variant links:

Genes affected

CHERP (HGNC:16930): (calcium homeostasis endoplasmic reticulum protein) Enables transmembrane transporter binding activity. Involved in positive regulation of calcineurin-NFAT signaling cascade and release of sequestered calcium ion into cytosol. Acts upstream of or within cellular calcium ion homeostasis and negative regulation of cell population proliferation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CHERP links:

C19orf44 (HGNC:26141): (chromosome 19 open reading frame 44)

C19orf44 links:

ENSG00000141979 (HGNC:):

ENSG00000141979 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23557964).

BS2

High AC in GnomAdExome4 at 161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHERP	NM_006387.6 link	c.2309G>A	p.Arg770His	missense_variant	Exon 14 of 17	ENST00000546361.7	NP_006378.3	Q8IWX8
C19orf44	NM_032207.4 link	c.*347C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000221671.8	NP_115583.1
C19orf44	XM_006722920.5 link	c.*347C>T		3_prime_UTR_variant	Exon 8 of 8		XP_006722983.1	M0R2B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHERP	ENST00000546361.7 link	c.2309G>A	p.Arg770His	missense_variant	Exon 14 of 17	1	NM_006387.6	ENSP00000439856.2	Q8IWX8
C19orf44	ENST00000221671.8 link	c.*347C>T		3_prime_UTR_variant	Exon 9 of 9	2	NM_032207.4	ENSP00000221671.2	Q9H6X5-1
ENSG00000141979	ENST00000409035.1 link	n.*194-1048G>A		intron_variant	Intron 6 of 11	2		ENSP00000386951.2	B8ZZF3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249428

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2309G>A (p.R770H) alteration is located in exon 14 (coding exon 14) of the CHERP gene. This alteration results from a G to A substitution at nucleotide position 2309, causing the arginine (R) at amino acid position 770 to be replaced by a histidine (H). 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

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;.

Eigen

Benign

-0.056

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.067

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.069

B;.

Vest4

0.47

MVP

0.36

MPC

1.0

ClinPred

0.50

GERP RS

4.7

Varity_R

0.24

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over