dbSNP rs6580: CALHM2:c.*35A>G (chr10-103447117-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_015916.5(CALHM2):c.*35A>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 0.383 in 1,546,426 control chromosomes in the GnomAD database, including 115,994 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 0.34 ( 9503 hom., cov: 33)

Exomes 𝑓: 0.39 ( 106491 hom. )

Consequence

CALHM2
NM_015916.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

32 publications found

Variant links:

Genes affected

CALHM2 (HGNC:23493): (calcium homeostasis modulator family member 2) Predicted to enable cation channel activity. Involved in positive regulation of apoptotic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CALHM2 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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM2	NM_015916.5 link	c.*35A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000260743.10	NP_057000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM2	ENST00000260743.10 link	c.*35A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_015916.5	ENSP00000260743.5
CALHM2	ENST00000369788.7 link	c.*35A>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000358803.3

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51757

AN:

152004

Hom.:

9497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.356

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.382

AC:

80164

AN:

209942

AF XY:

0.392

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.347

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.390

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.387

AC:

539887

AN:

1394304

Hom.:

106491

Cov.:

AF XY:

0.391

AC XY:

268682

AN XY:

687082

show subpopulations

African (AFR)

AF:

0.182

AC:

5740

AN:

31522

American (AMR)

AF:

0.354

AC:

13003

AN:

36768

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

7854

AN:

22138

East Asian (EAS)

AF:

0.353

AC:

13761

AN:

38970

South Asian (SAS)

AF:

0.504

AC:

38684

AN:

76800

European-Finnish (FIN)

AF:

0.441

AC:

22635

AN:

51284

Middle Eastern (MID)

AF:

0.335

AC:

1811

AN:

5414

European-Non Finnish (NFE)

AF:

0.386

AC:

414560

AN:

1073948

Other (OTH)

AF:

0.380

AC:

21839

AN:

57460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

17059

34119

51178

68238

85297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13228

26456

39684

52912

66140

<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:

0.340

AC:

51786

AN:

152122

Hom.:

9503

Cov.:

AF XY:

0.346

AC XY:

25711

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.195

AC:

8116

AN:

41536

American (AMR)

AF:

0.358

AC:

5479

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3472

East Asian (EAS)

AF:

0.357

AC:

1843

AN:

5166

South Asian (SAS)

AF:

0.497

AC:

2393

AN:

4818

European-Finnish (FIN)

AF:

0.454

AC:

4794

AN:

10560

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26788

AN:

67968

Other (OTH)

AF:

0.348

AC:

734

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1746

3491

5237

6982

8728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.376

Hom.:

19762

Bravo

AF:

0.323

Asia WGS

AF:

0.422

AC:

1465

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.5

(source)

DANN

Benign

0.60

PhyloP100

-1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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