10-103455259-A-G

Variant names:

• chr10-103455259-A-G
• rs2986016
• NM_001001412.4:c.*3T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001412.4(CALHM1):​c.*3T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,588,918 control chromosomes in the GnomAD database, including 480,859 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 0.82 (51367 hom., cov: 35)
  • Exomes 𝑓: 0.77 (429492 hom.)
• Consequence: CALHM1 NM_001001412.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM1	NM_001001412.4	MANE Select	c.*3T>C		3_prime_UTR	Exon 2 of 2	NP_001001412.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM1	ENST00000329905.6	TSL:1 MANE Select	c.*3T>C		3_prime_UTR	Exon 2 of 2	ENSP00000329926.6
	ENSG00000234699	ENST00000411906.2	TSL:2	n.1170+2023A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124352 AN: 152186 Hom.: 51306 Cov.: 35

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.794

GnomAD2 exomes AF: 0.803 AC: 173026 AN: 215588 AF XY: 0.800

Gnomad AFR exome AF: 0.941

Gnomad AMR exome AF: 0.845

Gnomad ASJ exome AF: 0.742

Gnomad EAS exome AF: 0.885

Gnomad FIN exome AF: 0.796

Gnomad NFE exome AF: 0.742

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.771 AC: 1108022 AN: 1436614 Hom.: 429492 Cov.: 76 AF XY: 0.772 AC XY: 550465 AN XY: 712640

African (AFR) AF: 0.942 AC: 31088 AN: 32992

American (AMR) AF: 0.840 AC: 35117 AN: 41794

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 18552 AN: 25004

East Asian (EAS) AF: 0.919 AC: 35673 AN: 38826

South Asian (SAS) AF: 0.873 AC: 72223 AN: 82772

European-Finnish (FIN) AF: 0.797 AC: 40871 AN: 51292

Middle Eastern (MID) AF: 0.736 AC: 4143 AN: 5630

European-Non Finnish (NFE) AF: 0.750 AC: 824032 AN: 1099020

Other (OTH) AF: 0.781 AC: 46323 AN: 59284

GnomAD4 genome AF: 0.817 AC: 124475 AN: 152304 Hom.: 51367 Cov.: 35 AF XY: 0.820 AC XY: 61061 AN XY: 74458

African (AFR) AF: 0.937 AC: 38950 AN: 41584

American (AMR) AF: 0.808 AC: 12369 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2553 AN: 3472

East Asian (EAS) AF: 0.889 AC: 4602 AN: 5176

South Asian (SAS) AF: 0.874 AC: 4222 AN: 4830

European-Finnish (FIN) AF: 0.801 AC: 8501 AN: 10610

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50744 AN: 68010

Other (OTH) AF: 0.794 AC: 1680 AN: 2116

Alfa AF: 0.767 Hom.: 61547

Bravo AF: 0.822

Asia WGS AF: 0.900 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-1.4
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: rs2986016; hg19: chr10-105215016;