Variant 10-103458295-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001001412.4(CALHM1):c.457G>A(p.Ala153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,611,950 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 18 hom. )

Consequence

CALHM1
NM_001001412.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

Variant links:

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]

CALHM1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020844638).

BP6

Variant 10-103458295-C-T is Benign according to our data. Variant chr10-103458295-C-T is described in ClinVar as [Benign]. Clinvar id is 781217.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00852 (1298/152326) while in subpopulation AFR AF= 0.0279 (1161/41568). AF 95% confidence interval is 0.0266. There are 16 homozygotes in gnomad4. There are 627 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALHM1	NM_001001412.4 linkuse as main transcript	c.457G>A	p.Ala153Thr	missense_variant	1/2	ENST00000329905.6
LOC124902494	XR_007062275.1 linkuse as main transcript	n.795-4135C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALHM1	ENST00000329905.6 linkuse as main transcript	c.457G>A	p.Ala153Thr	missense_variant	1/2	1	NM_001001412.4	P1
	ENST00000411906.1 linkuse as main transcript	n.392-4135C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00851

AC:

1295

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00276

AC:

666

AN:

241274

Hom.:

AF XY:

0.00217

AC XY:

286

AN XY:

131740

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.00219

GnomAD4 exome

AF:

0.00120

AC:

1747

AN:

1459624

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

783

AN XY:

726142

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00985

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000226

Gnomad4 OTH exome

AF:

0.00293

GnomAD4 genome

AF:

0.00852

AC:

1298

AN:

152326

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

627

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00964

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.000933

AC:

ExAC

AF:

0.00302

AC:

365

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.013

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.18

REVEL

Benign

0.058

Sift

Benign

0.58

Sift4G

Benign

0.58

Polyphen

0.0080

Vest4

0.051

MVP

0.030

MPC

0.15

ClinPred

0.0027

GERP RS

3.6

Varity_R

0.046

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over