rs3824

chr7-129213012-C-Gchr7-129213012-C-T

Variant summary

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

The NM_005631.5(SMO):c.*561C>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 0.14 in 261,698 control chromosomes in the GnomAD database, including 2,803 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 (1580 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1223 hom.)
• Consequence: SMO NM_005631.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=-0.83).
• 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	UniProt
SMO	NM_005631.5	c.*561C>G		3_prime_UTR_variant	12/12	ENST00000249373.8
SMO	XM_047420759.1	c.*561C>G		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.*561C>G		3_prime_UTR_variant	12/12	1	NM_005631.5	P1
	ENST00000466717.1	n.129+405G>C		intron_variant, non_coding_transcript_variant		3
SMO	ENST00000655644.1	c.*2680C>G		3_prime_UTR_variant, NMD_transcript_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21246 AN: 152076 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.139 AC: 15267 AN: 109504 Hom.: 1223 Cov.: 0 AF XY: 0.138 AC XY: 7219 AN XY: 52198

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152194 Hom.: 1580 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74414

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.137

Alfa AF: 0.0502 Hom.: 51

Bravo AF: 0.140

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.39

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: rs3824; hg19: chr7-128852853;