rs781144271

Variant names:

• chr10-103455348-C-G
• rs781144271
• NM_001001412.4:c.955G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-103455348-C-G
• chr10-103455348-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001412.4(CALHM1):​c.955G>C​(p.Glu319Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CALHM1 NM_001001412.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044727683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM1	NM_001001412.4	c.955G>C	p.Glu319Gln	missense_variant	Exon 2 of 2	ENST00000329905.6	NP_001001412.3
LOC124902494	XR_007062275.1	n.794+2112C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905.6	c.955G>C	p.Glu319Gln	missense_variant	Exon 2 of 2	1	NM_001001412.4	ENSP00000329926.6
ENSG00000234699	ENST00000411906.1	n.391+2112C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461142 Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2 AN XY: 726938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.63
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.029
Sift	Benign	0.51	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.099		Gain of MoRF binding (P = 0.1175);
MVP		0.067
MPC		0.16
ClinPred		0.060	T
GERP RS		2.7
Varity_R		0.12
gMVP		0.23

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: rs781144271; hg19: chr10-105215105;