Variant 19-16520170-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006387.6(CHERP):c.2441G>A(p.Arg814Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

CHERP
NM_006387.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

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:

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=0.19147599).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHERP	NM_006387.6 linkuse as main transcript	c.2441G>A	p.Arg814Gln	missense_variant	15/17	ENST00000546361.7	NP_006378.3
C19orf44	NM_032207.4 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	9/9	ENST00000221671.8	NP_115583.1
C19orf44	XM_006722920.5 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	8/8		XP_006722983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHERP	ENST00000546361.7 linkuse as main transcript	c.2441G>A	p.Arg814Gln	missense_variant	15/17	1	NM_006387.6	ENSP00000439856	P3
C19orf44	ENST00000221671.8 linkuse as main transcript	c.*117C>T		3_prime_UTR_variant	9/9	2	NM_032207.4	ENSP00000221671	P1	Q9H6X5-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152214

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248272

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000883

AC:

129

AN:

1460498

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74492

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 21, 2022

The c.2441G>A (p.R814Q) alteration is located in exon 15 (coding exon 15) of the CHERP gene. This alteration results from a G to A substitution at nucleotide position 2441, causing the arginine (R) at amino acid position 814 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.050

Sift

Benign

0.24

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.99

D;.

Vest4

0.31

MVP

0.56

MPC

0.93

ClinPred

0.23

GERP RS

3.8

Varity_R

0.14

gMVP

0.41

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

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