rs6492998

Variant names:

• chr15-41254433-G-A
• rs6492998
• NM_007236.5:c.141-2477G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-41254433-G-A
• chr15-41254433-G-C
• chr15-41254433-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.88).
• 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 rank	MANE	Protein	UniProt
CHP1	NM_007236.5	c.141-2477G>A		intron_variant	Intron 2 of 6	ENST00000334660.10	NP_009167.1
CHP1	XM_017021879.3	c.141-2477G>A		intron_variant	Intron 2 of 4		XP_016877368.1
CHP1	XM_047432125.1	c.-109-2477G>A		intron_variant	Intron 1 of 5		XP_047288081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHP1	ENST00000334660.10	c.141-2477G>A		intron_variant	Intron 2 of 6	1	NM_007236.5	ENSP00000335632.5

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

African (AFR) AF: 0.899 AC: 37354 AN: 41546

American (AMR) AF: 0.687 AC: 10502 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1890 AN: 3472

East Asian (EAS) AF: 0.762 AC: 3951 AN: 5182

South Asian (SAS) AF: 0.748 AC: 3612 AN: 4830

European-Finnish (FIN) AF: 0.475 AC: 5025 AN: 10584

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34567 AN: 67988

Other (OTH) AF: 0.613 AC: 1292 AN: 2108

Alfa AF: 0.554 Hom.: 47740

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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6492998; hg19: chr15-41546631;