10-103458602-T-C

Variant names:

• chr10-103458602-T-C
• rs2986018
• NM_001001412.4:c.150A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001001412.4(CALHM1):​c.150A>G​(p.Ala50Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 1,613,886 control chromosomes in the GnomAD database, including 503,667 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 0.83 (52440 hom., cov: 34)
  • Exomes 𝑓: 0.78 (451227 hom.)
• Consequence: CALHM1 NM_001001412.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 22 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-1.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

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.150A>G	p.Ala50Ala	synonymous	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.150A>G	p.Ala50Ala	synonymous	Exon 1 of 2	ENSP00000329926.6	Q8IU99
	ENSG00000234699	ENST00000411906.2	TSL:2	n.1171-3828T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125697 AN: 152158 Hom.: 52377 Cov.: 34

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.800

GnomAD2 exomes AF: 0.812 AC: 203819 AN: 251056 AF XY: 0.810

Gnomad AFR exome AF: 0.945

Gnomad AMR exome AF: 0.851

Gnomad ASJ exome AF: 0.754

Gnomad EAS exome AF: 0.884

Gnomad FIN exome AF: 0.815

Gnomad NFE exome AF: 0.757

Gnomad OTH exome AF: 0.789

GnomAD4 exome AF: 0.784 AC: 1145811 AN: 1461610 Hom.: 451227 Cov.: 93 AF XY: 0.785 AC XY: 570776 AN XY: 727130

African (AFR) AF: 0.946 AC: 31671 AN: 33480

American (AMR) AF: 0.847 AC: 37891 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 19681 AN: 26136

East Asian (EAS) AF: 0.918 AC: 36432 AN: 39698

South Asian (SAS) AF: 0.878 AC: 75706 AN: 86256

European-Finnish (FIN) AF: 0.813 AC: 43213 AN: 53158

Middle Eastern (MID) AF: 0.751 AC: 4330 AN: 5768

European-Non Finnish (NFE) AF: 0.764 AC: 849020 AN: 1112002

Other (OTH) AF: 0.793 AC: 47867 AN: 60390

GnomAD4 genome AF: 0.826 AC: 125822 AN: 152276 Hom.: 52440 Cov.: 34 AF XY: 0.829 AC XY: 61733 AN XY: 74462

African (AFR) AF: 0.940 AC: 39080 AN: 41588

American (AMR) AF: 0.814 AC: 12466 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2582 AN: 3468

East Asian (EAS) AF: 0.888 AC: 4586 AN: 5164

South Asian (SAS) AF: 0.877 AC: 4234 AN: 4828

European-Finnish (FIN) AF: 0.818 AC: 8673 AN: 10606

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51652 AN: 67994

Other (OTH) AF: 0.800 AC: 1692 AN: 2116

Alfa AF: 0.782 Hom.: 56707

Bravo AF: 0.831

Asia WGS AF: 0.902 AC: 3137 AN: 3478

EpiCase AF: 0.754

EpiControl AF: 0.754

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.089
DANN	Benign	0.35
PhyloP100		-1.3
PromoterAI		0.088	Neutral
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: rs2986018; hg19: chr10-105218359; COSMIC: COSV61708018;