15-41278827-A-C

Variant names:

• chr15-41278827-A-C
• NM_007236.5:c.472A>C
• CHP1 p.Arg158Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_007236.5(CHP1):​c.472A>C​(p.Arg158Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R158R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHP1 NM_007236.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.67 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP1	NM_007236.5	MANE Select	c.472A>C	p.Arg158Arg	synonymous	Exon 6 of 7	NP_009167.1	Q99653

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP1	ENST00000334660.10	TSL:1 MANE Select	c.472A>C	p.Arg158Arg	synonymous	Exon 6 of 7	ENSP00000335632.5	Q99653
	CHP1	ENST00000560411.5	TSL:1	n.*237A>C		non_coding_transcript_exon	Exon 5 of 6	ENSP00000453375.1	H0YLX1
	CHP1	ENST00000560411.5	TSL:1	n.*237A>C		3_prime_UTR	Exon 5 of 6	ENSP00000453375.1	H0YLX1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-41571025;