7-129206487-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005631.5(SMO):c.1164G>C(p.Gly388Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,613,838 control chromosomes in the GnomAD database, including 546,321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47490 hom., cov: 31)

Exomes 𝑓: 0.83 ( 498831 hom. )

Consequence

SMO
NM_005631.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.17

Publications

33 publications found

Variant links:

Genes affected

SMO (HGNC:11119): (smoothened, frizzled class receptor) The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

SMO Gene-Disease associations (from GenCC):

Curry-Jones syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
congenital hypothalamic hamartoma syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen
Hirschsprung disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SMO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-129206487-G-C is Benign according to our data. Variant chr7-129206487-G-C is described in ClinVar as Benign. ClinVar VariationId is 403462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5 link	c.1164G>C	p.Gly388Gly	synonymous_variant	Exon 6 of 12	ENST00000249373.8	NP_005622.1	Q99835
SMO	XM_047420759.1 link	c.774G>C	p.Gly258Gly	synonymous_variant	Exon 7 of 13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8 link	c.1164G>C	p.Gly388Gly	synonymous_variant	Exon 6 of 12	1	NM_005631.5	ENSP00000249373.3		Q99835

Frequencies

GnomAD3 genomes

AF:

0.787

AC:

119557

AN:

151978

Hom.:

47468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.956

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.844

Gnomad OTH

AF:

0.819

GnomAD2 exomes

AF:

0.798

AC:

200632

AN:

251400

AF XY:

0.803

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.869

Gnomad EAS exome

AF:

0.768

Gnomad FIN exome

AF:

0.812

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.833

GnomAD4 exome

AF:

0.825

AC:

1205966

AN:

1461742

Hom.:

498831

Cov.:

AF XY:

0.825

AC XY:

599792

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.684

AC:

22887

AN:

33476

American (AMR)

AF:

0.728

AC:

32559

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

22877

AN:

26136

East Asian (EAS)

AF:

0.745

AC:

29578

AN:

39698

South Asian (SAS)

AF:

0.769

AC:

66297

AN:

86246

European-Finnish (FIN)

AF:

0.807

AC:

43098

AN:

53404

Middle Eastern (MID)

AF:

0.879

AC:

5068

AN:

5768

European-Non Finnish (NFE)

AF:

0.840

AC:

934101

AN:

1111912

Other (OTH)

AF:

0.820

AC:

49501

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12346

24692

37037

49383

61729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21054

42108

63162

84216

105270

<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:

0.787

AC:

119629

AN:

152096

Hom.:

47490

Cov.:

AF XY:

0.783

AC XY:

58254

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.691

AC:

28663

AN:

41474

American (AMR)

AF:

0.745

AC:

11391

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

3037

AN:

3470

East Asian (EAS)

AF:

0.754

AC:

3892

AN:

5160

South Asian (SAS)

AF:

0.768

AC:

3699

AN:

4818

European-Finnish (FIN)

AF:

0.824

AC:

8717

AN:

10578

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.844

AC:

57371

AN:

67984

Other (OTH)

AF:

0.816

AC:

1727

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1279

2559

3838

5118

6397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.837

Hom.:

16960

Bravo

AF:

0.779

Asia WGS

AF:

0.730

AC:

2538

AN:

3478

EpiCase

AF:

0.850

EpiControl

AF:

0.846

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Hamartoma of hypothalamus

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.3

(source)

DANN

Benign

0.77

PhyloP100

1.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over