rs6492998

chr15-41254433-G-Achr15-41254433-G-Cchr15-41254433-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007236.5(CHP1):c.141-2477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,196 control chromosomes in the GnomAD database, including 34,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (34407 hom., cov: 33)
• Consequence: CHP1 NM_007236.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHP1	NM_007236.5	c.141-2477G>A		intron_variant		ENST00000334660.10
CHP1	XM_017021879.3	c.141-2477G>A		intron_variant
CHP1	XM_047432125.1	c.-109-2477G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHP1	ENST00000334660.10	c.141-2477G>A		intron_variant		1	NM_007236.5	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98583 AN: 152078 Hom.: 34333 Cov.: 33

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98715 AN: 152196 Hom.: 34407 Cov.: 33 AF XY: 0.651 AC XY: 48427 AN XY: 74406

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.613

Alfa AF: 0.546 Hom.: 33839

Bravo AF: 0.673

Asia WGS AF: 0.779 AC: 2708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.2
Dann	Benign	0.37

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

Other links and lift over

dbSNP: rs6492998; hg19: chr15-41546631;