rs2986016

Positions:

• chr10-103455259-A-G
• chr10-103455259-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000329905.6(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 ENST00000329905.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM1	NM_001001412.4	c.*3T>C		3_prime_UTR_variant	2/2	ENST00000329905.6	NP_001001412.3
LOC124902494	XR_007062275.1	n.794+2023A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905.6	c.*3T>C		3_prime_UTR_variant	2/2	1	NM_001001412.4	ENSP00000329926	P1
	ENST00000411906.1	n.391+2023A>G		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.803 AC: 173026 AN: 215588 Hom.: 69925 AF XY: 0.800 AC XY: 93704 AN XY: 117062

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 SAS exome AF: 0.876

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

Gnomad4 AFR exome AF: 0.942

Gnomad4 AMR exome AF: 0.840

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.919

Gnomad4 SAS exome AF: 0.873

Gnomad4 FIN exome AF: 0.797

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.781

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

Gnomad4 AFR AF: 0.937

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.801

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.794

Alfa AF: 0.762 Hom.: 47193

Bravo AF: 0.822

Asia WGS AF: 0.900 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.46

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: rs2986016; hg19: chr10-105215016;