NM_001001412.4:c.257T>G

Variant names:

• chr10-103458495-A-C
• rs2986017
• NM_001001412.4:c.257T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001412.4(CALHM1):​c.257T>G​(p.Leu86Arg) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CALHM1 NM_001001412.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 103 publications found

Genes affected

CALHM1 (HGNC:23494): (calcium homeostasis modulator 1) This gene encodes a calcium channel that plays a role in processing of amyloid-beta precursor protein. A polymorphism at this locus has been reported to be associated with susceptibility to late-onset Alzheimer's disease in some populations, but the pathogenicity of this polymorphism is unclear.[provided by RefSeq, Mar 2010]

ENSG00000234699 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048471272).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001412.4. 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
	CALHM1	NM_001001412.4	MANE Select	c.257T>G	p.Leu86Arg	missense	Exon 1 of 2	NP_001001412.3	Q8IU99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM1	ENST00000329905.6	TSL:1 MANE Select	c.257T>G	p.Leu86Arg	missense	Exon 1 of 2	ENSP00000329926.6	Q8IU99
	ENSG00000234699	ENST00000411906.2	TSL:2	n.1171-3935A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 42856

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.4
DANN	Benign	0.81
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.16
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.027
Sift	Benign	0.46	T
Sift4G	Benign	0.28	T
Polyphen		0.014	B
Vest4		0.035
MutPred		0.30		Gain of disorder (P = 0.0134)
MVP		0.16
MPC		0.23
ClinPred		0.023	T
GERP RS		1.4
PromoterAI		-0.019	Neutral
Varity_R		0.055
gMVP		0.53
Mutation Taster		=99/1	polymorphism

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: rs2986017; hg19: chr10-105218252;