rs1061280

Positions:

• chr7-129213282-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005631.5(SMO):​c.*831A>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 0.148 in 232,984 control chromosomes in the GnomAD database, including 2,781 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 0.15 (1806 hom., cov: 31)
  • Exomes 𝑓: 0.14 (975 hom.)
• Consequence: SMO NM_005631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5	c.*831A>G		3_prime_UTR_variant	12/12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.*831A>G		3_prime_UTR_variant	13/13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8	c.*831A>G		3_prime_UTR_variant	12/12	1	NM_005631.5	ENSP00000249373	P1
	ENST00000466717.1	n.129+135T>C		intron_variant, non_coding_transcript_variant		3
SMO	ENST00000655644.1	c.*2950A>G		3_prime_UTR_variant, NMD_transcript_variant	12/12			ENSP00000499377

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22706 AN: 152008 Hom.: 1794 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.145 AC: 11697 AN: 80858 Hom.: 975 Cov.: 0 AF XY: 0.144 AC XY: 5344 AN XY: 37180

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.150 AC: 22747 AN: 152126 Hom.: 1806 Cov.: 31 AF XY: 0.153 AC XY: 11417 AN XY: 74388

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.149

Alfa AF: 0.129 Hom.: 2254

Bravo AF: 0.151

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.78

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: rs1061280; hg19: chr7-128853123;