10-103458602-T-C

Position:

• chr10-103458602-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001001412.4(CALHM1):​c.150A>G​(p.Ala50=) 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALHM1	NM_001001412.4	c.150A>G	p.Ala50=	synonymous_variant	1/2	ENST00000329905.6
LOC124902494	XR_007062275.1	n.795-3828T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALHM1	ENST00000329905.6	c.150A>G	p.Ala50=	synonymous_variant	1/2	1	NM_001001412.4	P1
	ENST00000411906.1	n.392-3828T>C		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.812 AC: 203819 AN: 251056 Hom.: 83353 AF XY: 0.810 AC XY: 110004 AN XY: 135842

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 SAS exome AF: 0.879

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

Gnomad4 AFR exome AF: 0.946

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.918

Gnomad4 SAS exome AF: 0.878

Gnomad4 FIN exome AF: 0.813

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.793

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

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.800

Alfa AF: 0.780 Hom.: 39993

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.089
DANN	Benign	0.35

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: rs2986018; hg19: chr10-105218359; COSMIC: COSV61708018;