Genetic Variant CALHM6:p.Pro110Pro (chr6-116462259-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001010919.3(CALHM6):c.330C>T(p.Pro110Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,378,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

CALHM6
NM_001010919.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.90

Publications

0 publications found

Variant links:

Genes affected

CALHM6 (HGNC:33391): (calcium homeostasis modulator family member 6) Predicted to enable cation channel activity. Predicted to be involved in cation transmembrane transport. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CALHM6 links:

ENSG00000285446 (HGNC:):

ENSG00000285446 links:

CALHM6-AS1 (HGNC:40971): (CALHM6 antisense RNA 1)

CALHM6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 6-116462259-C-T is Benign according to our data. Variant chr6-116462259-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656864.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALHM6	NM_001010919.3	MANE Select	c.330C>T	p.Pro110Pro	synonymous	Exon 2 of 3	NP_001010919.1	Q5R3K3-1
CALHM6	NM_001276460.2		c.9+830C>T		intron	N/A	NP_001263389.1	Q5R3K3-2
CALHM6-AS1	NR_174951.1		n.87-1065G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALHM6	ENST00000368605.3	TSL:5 MANE Select	c.330C>T	p.Pro110Pro	synonymous	Exon 2 of 3	ENSP00000357594.1	Q5R3K3-1
ENSG00000285446	ENST00000644499.1		c.767-1024C>T		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1
CALHM6	ENST00000859968.1		c.330C>T	p.Pro110Pro	synonymous	Exon 1 of 2	ENSP00000530027.1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000442

AC:

AN:

13580

AF XY:

0.000499

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000963

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000386

AC:

474

AN:

1226538

Hom.:

Cov.:

AF XY:

0.000412

AC XY:

245

AN XY:

594810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24448

American (AMR)

AF:

0.000398

AC:

AN:

12556

Ashkenazi Jewish (ASJ)

AF:

0.0000572

AC:

AN:

17490

East Asian (EAS)

AF:

0.00

AC:

AN:

27396

South Asian (SAS)

AF:

0.0000362

AC:

AN:

55208

European-Finnish (FIN)

AF:

0.0000669

AC:

AN:

29912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3514

European-Non Finnish (NFE)

AF:

0.000451

AC:

453

AN:

1005372

Other (OTH)

AF:

0.000217

AC:

AN:

50642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

116

145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000342

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41454

American (AMR)

AF:

0.000327

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000216

Hom.:

Bravo

AF:

0.000340

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-2.9

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over