rs35641939

Variant names:

• chr16-23756415-G-A
• rs35641939
• NM_022097.4:c.380G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-23756415-G-A
• chr16-23756415-G-C
• chr16-23756415-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022097.4(CHP2):​c.380G>A​(p.Arg127His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,784 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 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: CHP2 NM_022097.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 5 publications found

Genes affected

CHP2 (HGNC:24927): (calcineurin like EF-hand protein 2) This gene product is a small calcium-binding protein that regulates cell pH by controlling plasma membrane-type Na+/H+ exchange activity. This protein shares sequence similarity with calcineurin B and can bind to and stimulate the protein phosphatase activity of calcineurin A (CnA) and functions in the calcineurin/NFAT (nuclear factor of activated T cells) signaling pathway. Another member of the CHP subfamily, Calcineurin B homologous protein 1, is located on Chromosome 15 and is an inhibitor of calcineurin activity and has a genetic phenotype associated with Parkinson's Disease (OMIM:606988). This gene was initially identified as a tumor-associated antigen and was previously referred to as Hepatocellular carcinoma-associated antigen 520. [provided by RefSeq, Jul 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.12649307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022097.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP2	NM_022097.4	MANE Select	c.380G>A	p.Arg127His	missense	Exon 5 of 7	NP_071380.1	O43745

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP2	ENST00000300113.3	TSL:1 MANE Select	c.380G>A	p.Arg127His	missense	Exon 5 of 7	ENSP00000300113.2	O43745
	CHP2	ENST00000871596.1		c.404G>A	p.Arg135His	missense	Exon 5 of 7	ENSP00000541655.1
	CHP2	ENST00000871595.1		c.377G>A	p.Arg126His	missense	Exon 5 of 7	ENSP00000541654.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152040 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251262 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000958 AC: 140 AN: 1461744 Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1111944

Other (OTH) AF: 0.0000994 AC: 6 AN: 60386

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74280

African (AFR) AF: 0.0000242 AC: 1 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15254

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000430 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.068
Sift	Benign	0.082	T
Sift4G	Benign	0.13	T
Polyphen		0.094	B
Vest4		0.34
MVP		0.68
MPC		0.49
ClinPred		0.066	T
GERP RS		2.9
Varity_R		0.30
gMVP		0.36
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs35641939; hg19: chr16-23767736; COSMIC: COSV55649738; COSMIC: COSV55649738;