7-129206487-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005631.5(SMO):c.1164G>C(p.Gly388=) 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:3

Conservation

PhyloP100: 1.17

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.1164G>C	p.Gly388=	synonymous_variant	6/12	ENST00000249373.8
SMO	XM_047420759.1 linkuse as main transcript	c.774G>C	p.Gly258=	synonymous_variant	7/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMO	ENST00000249373.8 linkuse as main transcript	c.1164G>C	p.Gly388=	synonymous_variant	6/12	1	NM_005631.5	P1
SMO	ENST00000495998.1 linkuse as main transcript	n.109G>C		non_coding_transcript_exon_variant	2/3	3
SMO	ENST00000462420.2 linkuse as main transcript	c.246G>C	p.Gly82=	synonymous_variant, NMD_transcript_variant	2/5	4
SMO	ENST00000655644.1 linkuse as main transcript	c.*1028G>C		3_prime_UTR_variant, NMD_transcript_variant	7/12

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

GnomAD3 exomes

AF:

0.798

AC:

200632

AN:

251400

Hom.:

80651

AF XY:

0.803

AC XY:

109062

AN XY:

135864

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 SAS exome

AF:

0.766

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

Gnomad4 AFR exome

AF:

0.684

Gnomad4 AMR exome

AF:

0.728

Gnomad4 ASJ exome

AF:

0.875

Gnomad4 EAS exome

AF:

0.745

Gnomad4 SAS exome

AF:

0.769

Gnomad4 FIN exome

AF:

0.807

Gnomad4 NFE exome

AF:

0.840

Gnomad4 OTH exome

AF:

0.820

GnomAD4 genome

AF:

0.787

AC:

119629

AN:

152096

Hom.:

47490

Cov.:

AF XY:

0.783

AC XY:

58254

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.754

Gnomad4 SAS

AF:

0.768

Gnomad4 FIN

AF:

0.824

Gnomad4 NFE

AF:

0.844

Gnomad4 OTH

AF:

0.816

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

Cadd

Benign

8.3

Dann

Benign

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over