rs1061285

Positions:

• chr7-129213467-C-A
• chr7-129213467-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005631.5(SMO):​c.*1016C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 232,636 control chromosomes in the GnomAD database, including 2,526 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 0.14 (1578 hom., cov: 31)
  • Exomes 𝑓: 0.14 (948 hom.)
• Consequence: SMO NM_005631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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]

ENSG00000243230 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMO	NM_005631.5	c.*1016C>A		3_prime_UTR_variant	12/12	ENST00000249373.8	NP_005622.1
SMO	XM_047420759.1	c.*1016C>A		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.*1016C>A		3_prime_UTR_variant	12/12	1	NM_005631.5	ENSP00000249373.3
ENSG00000243230	ENST00000466717.1	n.79G>T		non_coding_transcript_exon_variant	1/2	3
SMO	ENST00000655644.1	n.*3135C>A		non_coding_transcript_exon_variant	12/12			ENSP00000499377.1
SMO	ENST00000655644.1	n.*3135C>A		3_prime_UTR_variant	12/12			ENSP00000499377.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21246 AN: 151944 Hom.: 1567 Cov.: 31

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.142 AC: 11457 AN: 80574 Hom.: 948 Cov.: 0 AF XY: 0.142 AC XY: 5260 AN XY: 37090

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.140 AC: 21286 AN: 152062 Hom.: 1578 Cov.: 31 AF XY: 0.144 AC XY: 10694 AN XY: 74310

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.138

Alfa AF: 0.116 Hom.: 1085

Bravo AF: 0.140

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	8.7
DANN	Benign	0.84

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: rs1061285; hg19: chr7-128853308;