rs1061285

Variant names:

• chr7-129213467-C-A
• rs1061285
• NM_005631.5:c.*1016C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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
• mosaic SMO syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital hypothalamic hamartoma syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, G2P
• 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMO	NM_005631.5	MANE Select	c.*1016C>A		3_prime_UTR	Exon 12 of 12	NP_005622.1	Q99835

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMO	ENST00000249373.8	TSL:1 MANE Select	c.*1016C>A		3_prime_UTR	Exon 12 of 12	ENSP00000249373.3	Q99835
	SMO	ENST00000925241.1		c.*1016C>A		3_prime_UTR	Exon 12 of 12	ENSP00000595300.1
	SMO	ENST00000925243.1		c.*1016C>A		3_prime_UTR	Exon 12 of 12	ENSP00000595302.1

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

African (AFR) AF: 0.139 AC: 537 AN: 3854

American (AMR) AF: 0.157 AC: 389 AN: 2472

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 544 AN: 5084

East Asian (EAS) AF: 0.250 AC: 2816 AN: 11276

South Asian (SAS) AF: 0.236 AC: 164 AN: 694

European-Finnish (FIN) AF: 0.128 AC: 60 AN: 468

Middle Eastern (MID) AF: 0.0868 AC: 42 AN: 484

European-Non Finnish (NFE) AF: 0.122 AC: 6026 AN: 49536

Other (OTH) AF: 0.131 AC: 879 AN: 6706

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

African (AFR) AF: 0.137 AC: 5676 AN: 41486

American (AMR) AF: 0.179 AC: 2727 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 404 AN: 3464

East Asian (EAS) AF: 0.251 AC: 1295 AN: 5168

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

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10556

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

European-Non Finnish (NFE) AF: 0.123 AC: 8386 AN: 67982

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.119 Hom.: 1473

Bravo AF: 0.140

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	8.7
DANN	Benign	0.84
PhyloP100		0.19
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: rs1061285; hg19: chr7-128853308;