chr15-41271752-A-G

Variant names:

• chr15-41271752-A-G
• rs28374715
• NM_007236.5:c.411+1134A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 publications found

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 Gene-Disease associations (from GenCC):

• spastic ataxia 9, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007236.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP1	NM_007236.5	MANE Select	c.411+1134A>G		intron	N/A	NP_009167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP1	ENST00000334660.10	TSL:1 MANE Select	c.411+1134A>G		intron	N/A	ENSP00000335632.5
	CHP1	ENST00000560411.5	TSL:1	n.*176+1134A>G		intron	N/A	ENSP00000453375.1
	CHP1	ENST00000560397.5	TSL:3	c.411+1134A>G		intron	N/A	ENSP00000454007.1

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

African (AFR) AF: 0.271 AC: 11231 AN: 41518

American (AMR) AF: 0.198 AC: 3029 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5180

South Asian (SAS) AF: 0.182 AC: 877 AN: 4826

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17813 AN: 67988

Other (OTH) AF: 0.235 AC: 497 AN: 2114

Alfa AF: 0.252 Hom.: 8842

Bravo AF: 0.243

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.35
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28374715; hg19: chr15-41563950;