dbSNP rs2986016: CALHM1:c.*3T>C (chr10-103455259-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001412.4(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
NM_001001412.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

18 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CALHM1	NM_001001412.4 link	c.*3T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000329905.6	NP_001001412.3	Q8IU99
LOC124902494	XR_007062275.1 link	n.794+2023A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM1	ENST00000329905.6 link	c.*3T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_001001412.4	ENSP00000329926.6		Q8IU99
ENSG00000234699	ENST00000411906.2 link	n.1170+2023A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124352

AN:

152186

Hom.:

51306

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.803

AC:

173026

AN:

215588

AF XY:

0.800

show subpopulations

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 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.:

AF XY:

0.772

AC XY:

550465

AN XY:

712640

show subpopulations

African (AFR)

AF:

0.942

AC:

31088

AN:

32992

American (AMR)

AF:

0.840

AC:

35117

AN:

41794

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

18552

AN:

25004

East Asian (EAS)

AF:

0.919

AC:

35673

AN:

38826

South Asian (SAS)

AF:

0.873

AC:

72223

AN:

82772

European-Finnish (FIN)

AF:

0.797

AC:

40871

AN:

51292

Middle Eastern (MID)

AF:

0.736

AC:

4143

AN:

5630

European-Non Finnish (NFE)

AF:

0.750

AC:

824032

AN:

1099020

Other (OTH)

AF:

0.781

AC:

46323

AN:

59284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15302

30605

45907

61210

76512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20326

40652

60978

81304

101630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.817

AC:

124475

AN:

152304

Hom.:

51367

Cov.:

AF XY:

0.820

AC XY:

61061

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.937

AC:

38950

AN:

41584

American (AMR)

AF:

0.808

AC:

12369

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.735

AC:

2553

AN:

3472

East Asian (EAS)

AF:

0.889

AC:

4602

AN:

5176

South Asian (SAS)

AF:

0.874

AC:

4222

AN:

4830

European-Finnish (FIN)

AF:

0.801

AC:

8501

AN:

10610

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.746

AC:

50744

AN:

68010

Other (OTH)

AF:

0.794

AC:

1680

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1177

2355

3532

4710

5887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.767

Hom.:

61547

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

(source)

DANN

Benign

0.46

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over