rs9568

Positions:

• chr15-41281414-C-A

Variant summary

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

The ENST00000334660.10(CHP1):​c.*2025C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,540 control chromosomes in the GnomAD database, including 4,846 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 (4835 hom., cov: 32)
  • Exomes 𝑓: 0.24 (11 hom.)
• Consequence: CHP1 ENST00000334660.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHP1	NM_007236.5	c.*2025C>A		3_prime_UTR_variant	7/7	ENST00000334660.10	NP_009167.1
CHP1	XM_047432124.1	c.*2025C>A		3_prime_UTR_variant	6/6		XP_047288080.1
CHP1	XM_047432125.1	c.*2025C>A		3_prime_UTR_variant	6/6		XP_047288081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHP1	ENST00000334660.10	c.*2025C>A		3_prime_UTR_variant	7/7	1	NM_007236.5	ENSP00000335632	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37456 AN: 151984 Hom.: 4828 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.245

GnomAD4 exome AF: 0.237 AC: 104 AN: 438 Hom.: 11 Cov.: 0 AF XY: 0.231 AC XY: 61 AN XY: 264

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.246 AC: 37485 AN: 152102 Hom.: 4835 Cov.: 32 AF XY: 0.245 AC XY: 18245 AN XY: 74348

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.244

Alfa AF: 0.248 Hom.: 1966

Bravo AF: 0.242

Asia WGS AF: 0.144 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.45

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: rs9568; hg19: chr15-41573612; COSMIC: COSV58157185; COSMIC: COSV58157185;