Genetic Variant CALHM1:c.*87A>G (chr10-103455175-T-C) – 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.*87A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,471,828 control chromosomes in the GnomAD database, including 85,278 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 0.35 ( 9534 hom., cov: 33)

Exomes 𝑓: 0.34 ( 75744 hom. )

Consequence

CALHM1
NM_001001412.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.787

Publications

20 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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001412.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM1	NM_001001412.4	MANE Select	c.*87A>G		3_prime_UTR	Exon 2 of 2	NP_001001412.3	Q8IU99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM1	ENST00000329905.6	TSL:1 MANE Select	c.*87A>G		3_prime_UTR	Exon 2 of 2	ENSP00000329926.6	Q8IU99
	ENSG00000234699	ENST00000411906.2	TSL:2	n.1170+1939T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53312

AN:

151786

Hom.:

9516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.330

GnomAD4 exome

AF:

0.336

AC:

444117

AN:

1319924

Hom.:

75744

Cov.:

AF XY:

0.334

AC XY:

214883

AN XY:

643796

show subpopulations

African (AFR)

AF:

0.404

AC:

11854

AN:

29360

American (AMR)

AF:

0.437

AC:

11458

AN:

26226

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

6213

AN:

20140

East Asian (EAS)

AF:

0.473

AC:

16667

AN:

35232

South Asian (SAS)

AF:

0.280

AC:

18681

AN:

66706

European-Finnish (FIN)

AF:

0.303

AC:

12078

AN:

39898

Middle Eastern (MID)

AF:

0.311

AC:

1554

AN:

4998

European-Non Finnish (NFE)

AF:

0.333

AC:

347266

AN:

1042626

Other (OTH)

AF:

0.335

AC:

18346

AN:

54738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

16145

32289

48434

64578

80723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11956

23912

35868

47824

59780

<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:

0.351

AC:

53372

AN:

151904

Hom.:

9534

Cov.:

AF XY:

0.351

AC XY:

26083

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.402

AC:

16631

AN:

41408

American (AMR)

AF:

0.397

AC:

6059

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1064

AN:

3462

East Asian (EAS)

AF:

0.433

AC:

2225

AN:

5144

South Asian (SAS)

AF:

0.290

AC:

1392

AN:

4808

European-Finnish (FIN)

AF:

0.296

AC:

3132

AN:

10584

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.321

AC:

21773

AN:

67916

Other (OTH)

AF:

0.332

AC:

699

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1825

3649

5474

7298

9123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.330

Hom.:

19002

Bravo

AF:

0.364

Asia WGS

AF:

0.380

AC:

1326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

-0.79

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over