10-103458497-C-T

Variant names:

• chr10-103458497-C-T
• rs4918016
• NM_001001412.4:c.255G>A

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.255G>A​(p.Pro85Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,612,786 control chromosomes in the GnomAD database, including 89,747 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 0.30 (7025 hom., cov: 33)
  • Exomes 𝑓: 0.33 (82722 hom.)
• Consequence: CALHM1 NM_001001412.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.11
• Publications: 14 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=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.255G>A	p.Pro85Pro	synonymous	Exon 1 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.255G>A	p.Pro85Pro	synonymous	Exon 1 of 2	ENSP00000329926.6
	ENSG00000234699	ENST00000411906.2	TSL:2	n.1171-3933C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45235 AN: 151946 Hom.: 7010 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.336 AC: 83019 AN: 246782 AF XY: 0.330

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.450

Gnomad ASJ exome AF: 0.314

Gnomad EAS exome AF: 0.441

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.334 AC: 487301 AN: 1460722 Hom.: 82722 Cov.: 83 AF XY: 0.331 AC XY: 240388 AN XY: 726694

African (AFR) AF: 0.208 AC: 6975 AN: 33480

American (AMR) AF: 0.440 AC: 19666 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8186 AN: 26114

East Asian (EAS) AF: 0.470 AC: 18643 AN: 39684

South Asian (SAS) AF: 0.280 AC: 24123 AN: 86250

European-Finnish (FIN) AF: 0.314 AC: 16482 AN: 52530

Middle Eastern (MID) AF: 0.319 AC: 1839 AN: 5764

European-Non Finnish (NFE) AF: 0.334 AC: 371684 AN: 1111862

Other (OTH) AF: 0.327 AC: 19703 AN: 60342

GnomAD4 genome AF: 0.298 AC: 45280 AN: 152064 Hom.: 7025 Cov.: 33 AF XY: 0.300 AC XY: 22290 AN XY: 74328

African (AFR) AF: 0.213 AC: 8850 AN: 41508

American (AMR) AF: 0.373 AC: 5691 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2203 AN: 5142

South Asian (SAS) AF: 0.285 AC: 1376 AN: 4826

European-Finnish (FIN) AF: 0.302 AC: 3192 AN: 10566

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.322 AC: 21861 AN: 67960

Other (OTH) AF: 0.302 AC: 638 AN: 2114

Alfa AF: 0.276 Hom.: 2158

Bravo AF: 0.303

Asia WGS AF: 0.365 AC: 1271 AN: 3478

EpiCase AF: 0.311

EpiControl AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.93
PhyloP100		-5.1
PromoterAI		-0.017	Neutral
Mutation Taster		=98/2	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: rs4918016; hg19: chr10-105218254; COSMIC: COSV61707617;