Variant chr15-41278763-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007236.5(CHP1):c.412-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,614,038 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 19 hom. )

Consequence

CHP1
NM_007236.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005050

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

CHP1 (HGNC:17433): (calcineurin like EF-hand protein 1) This gene encodes a phosphoprotein that binds to the Na+/H+ exchanger NHE1. This protein serves as an essential cofactor which supports the physiological activity of NHE family members and may play a role in the mitogenic regulation of NHE1. The protein shares similarity with calcineurin B and calmodulin and it is also known to be an endogenous inhibitor of calcineurin activity. [provided by RefSeq, Jul 2008]

CHP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 15-41278763-C-T is Benign according to our data. Variant chr15-41278763-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645189.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHP1	NM_007236.5 linkuse as main transcript	c.412-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000334660.10
CHP1	XM_047432124.1 linkuse as main transcript	c.163-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CHP1	XM_047432125.1 linkuse as main transcript	c.163-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHP1	ENST00000334660.10 linkuse as main transcript	c.412-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007236.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00291

AC:

443

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00501

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00291

AC:

732

AN:

251328

Hom.:

AF XY:

0.00303

AC XY:

411

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00432

AC:

6317

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

3146

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00248

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00516

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00291

AC:

443

AN:

152274

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00501

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00387

Hom.:

Bravo

AF:

0.00295

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00605

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

CHP1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.94

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.010

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