10-103458497-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM1	NM_001001412.4	c.255G>A	p.Pro85Pro	synonymous_variant	Exon 1 of 2	ENST00000329905.6	NP_001001412.3
LOC124902494	XR_007062275.1	n.795-3933C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905.6	c.255G>A	p.Pro85Pro	synonymous_variant	Exon 1 of 2	1	NM_001001412.4	ENSP00000329926.6
ENSG00000234699	ENST00000411906.1	n.392-3933C>T		intron_variant	Intron 1 of 1	2

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

GnomAD3 exomes AF: 0.336 AC: 83019 AN: 246782 Hom.: 14505 AF XY: 0.330 AC XY: 44380 AN XY: 134526

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 SAS exome AF: 0.283

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

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.313

Gnomad4 EAS exome AF: 0.470

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.327

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

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.302

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.93

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: rs4918016; hg19: chr10-105218254; COSMIC: COSV61707617;