rs28374715

Positions:

• chr15-41271752-A-G

Variant summary

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

The NM_007236.5(CHP1):​c.411+1134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,158 control chromosomes in the GnomAD database, including 4,789 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 0.25 (4789 hom., cov: 32)
• Consequence: CHP1 NM_007236.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHP1	NM_007236.5	c.411+1134A>G		intron_variant		ENST00000334660.10
CHP1	XM_047432124.1	c.162+1134A>G		intron_variant
CHP1	XM_047432125.1	c.162+1134A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHP1	ENST00000334660.10	c.411+1134A>G		intron_variant		1	NM_007236.5	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37625 AN: 152040 Hom.: 4789 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.247 AC: 37645 AN: 152158 Hom.: 4789 Cov.: 32 AF XY: 0.245 AC XY: 18205 AN XY: 74368

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.235

Alfa AF: 0.266 Hom.: 876

Bravo AF: 0.243

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28374715; hg19: chr15-41563950;