7-129189117-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005631.5(SMO):c.-35G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000733 in 1,203,812 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (5 hom.)
• Consequence: SMO NM_005631.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0530

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-129189117-G-T is Benign according to our data. Variant chr7-129189117-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00339 (515/151964) while in subpopulation AFR AF= 0.0116 (482/41526). AF 95% confidence interval is 0.0108. There are 4 homozygotes in gnomad4. There are 242 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5	c.-35G>T		5_prime_UTR_variant	1/12	ENST00000249373.8
SMO	XM_047420759.1	c.-539G>T		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.-35G>T		5_prime_UTR_variant	1/12	1	NM_005631.5	P1
SMO	ENST00000655644.1	c.-35G>T		5_prime_UTR_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 513 AN: 151856 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.000349 AC: 367 AN: 1051848 Hom.: 5 Cov.: 26 AF XY: 0.000346 AC XY: 172 AN XY: 496414

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000300

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.00339 AC: 515 AN: 151964 Hom.: 4 Cov.: 32 AF XY: 0.00326 AC XY: 242 AN XY: 74300

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00411

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	18
Dann	Benign	0.91
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.2

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

Other links and lift over

dbSNP: rs543363913; hg19: chr7-128828958;