rs1061280

Variant names:

• chr7-129213282-A-G
• rs1061280
• NM_005631.5:c.*831A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-129213282-A-G
• chr7-129213282-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• Curry-Jones syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P
• congenital hypothalamic hamartoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, ClinGen
• Hirschsprung disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000243230 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005631.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMO	NM_005631.5	MANE Select	c.*831A>G		3_prime_UTR	Exon 12 of 12	NP_005622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMO	ENST00000249373.8	TSL:1 MANE Select	c.*831A>G		3_prime_UTR	Exon 12 of 12	ENSP00000249373.3
	SMO	ENST00000655644.1		n.*2950A>G		non_coding_transcript_exon	Exon 12 of 12	ENSP00000499377.1
	SMO	ENST00000655644.1		n.*2950A>G		3_prime_UTR	Exon 12 of 12	ENSP00000499377.1

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

African (AFR) AF: 0.169 AC: 656 AN: 3890

American (AMR) AF: 0.160 AC: 400 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 550 AN: 5116

East Asian (EAS) AF: 0.251 AC: 2851 AN: 11380

South Asian (SAS) AF: 0.236 AC: 165 AN: 700

European-Finnish (FIN) AF: 0.100 AC: 6 AN: 60

Middle Eastern (MID) AF: 0.0918 AC: 45 AN: 490

European-Non Finnish (NFE) AF: 0.122 AC: 6099 AN: 49962

Other (OTH) AF: 0.137 AC: 925 AN: 6760

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

African (AFR) AF: 0.169 AC: 7030 AN: 41502

American (AMR) AF: 0.183 AC: 2797 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3466

East Asian (EAS) AF: 0.250 AC: 1289 AN: 5164

South Asian (SAS) AF: 0.221 AC: 1067 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1393 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8398 AN: 67988

Other (OTH) AF: 0.149 AC: 314 AN: 2108

Alfa AF: 0.133 Hom.: 5382

Bravo AF: 0.151

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1061280; hg19: chr7-128853123;