Variant 10-103455334-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001001412.4(CALHM1):c.969G>A(p.Met323Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,613,582 control chromosomes in the GnomAD database, including 446 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 21 hom., cov: 34)

Exomes 𝑓: 0.022 ( 425 hom. )

Consequence

CALHM1
NM_001001412.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.275

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:

ENSG00000234699 (HGNC:):

ENSG00000234699 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028559566).

BP6

Variant 10-103455334-C-T is Benign according to our data. Variant chr10-103455334-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0166 (2522/152380) while in subpopulation NFE AF= 0.0253 (1721/68040). AF 95% confidence interval is 0.0243. There are 21 homozygotes in gnomad4. There are 1162 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM1	NM_001001412.4 linkuse as main transcript	c.969G>A	p.Met323Ile	missense_variant	2/2	ENST00000329905.6	NP_001001412.3	Q8IU99
LOC124902494	XR_007062275.1 linkuse as main transcript	n.794+2098C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905.6 linkuse as main transcript	c.969G>A	p.Met323Ile	missense_variant	2/2	1	NM_001001412.4	ENSP00000329926.6		Q8IU99
ENSG00000234699	ENST00000411906.1 linkuse as main transcript	n.391+2098C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2520

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00702

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0160

AC:

4000

AN:

249428

Hom.:

AF XY:

0.0159

AC XY:

2152

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.00623

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00860

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00981

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0223

AC:

32545

AN:

1461202

Hom.:

425

Cov.:

AF XY:

0.0218

AC XY:

15820

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00606

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00724

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00943

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.0259

Gnomad4 OTH exome

AF:

0.0203

GnomAD4 genome

AF:

0.0166

AC:

2522

AN:

152380

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1162

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00702

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0253

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0153

TwinsUK

AF:

0.0251

AC:

ALSPAC

AF:

0.0246

AC:

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0200

AC:

172

ExAC

AF:

0.0169

AC:

2049

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0238

EpiControl

AF:

0.0240

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.010

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.33

REVEL

Benign

0.14

Sift

Benign

0.42

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.019

MutPred

0.30

Loss of disorder (P = 0.0511);

MPC

0.17

ClinPred

0.0042

GERP RS

3.7

Varity_R

0.22

gMVP

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over