rs56358283

Variant names:

• chr7-129206382-G-A
• rs56358283
• NM_005631.5:c.1140+13G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-129206382-G-A
• chr7-129206382-G-C
• chr7-129206382-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005631.5(SMO):​c.1140+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,104 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (21 hom.)
• Consequence: SMO NM_005631.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 1 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: G2P, PanelApp Australia
• mosaic SMO syndrome

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

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

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 7-129206382-G-A is Benign according to our data. Variant chr7-129206382-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 446018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (1577/152290) while in subpopulation AFR AF = 0.0352 (1461/41550). AF 95% confidence interval is 0.0337. There are 29 homozygotes in GnomAd4. There are 748 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR,AD gene

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.1140+13G>A		intron	N/A	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.1140+13G>A		intron	N/A	ENSP00000249373.3	Q99835
	SMO	ENST00000925241.1		c.1140+13G>A		intron	N/A	ENSP00000595300.1
	SMO	ENST00000925243.1		c.1140+13G>A		intron	N/A	ENSP00000595302.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1572 AN: 152172 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00271 AC: 681 AN: 251224 AF XY: 0.00194

Gnomad AFR exome AF: 0.0356

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00103 AC: 1500 AN: 1461814 Hom.: 21 Cov.: 34 AF XY: 0.000894 AC XY: 650 AN XY: 727214

African (AFR) AF: 0.0355 AC: 1187 AN: 33480

American (AMR) AF: 0.00237 AC: 106 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000674 AC: 75 AN: 1111946

Other (OTH) AF: 0.00205 AC: 124 AN: 60390

GnomAD4 genome AF: 0.0104 AC: 1577 AN: 152290 Hom.: 29 Cov.: 32 AF XY: 0.0100 AC XY: 748 AN XY: 74456

African (AFR) AF: 0.0352 AC: 1461 AN: 41550

American (AMR) AF: 0.00556 AC: 85 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68024

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00322 Hom.: 2

Bravo AF: 0.0119

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs56358283;

hg19: chr7-128846223;

COSMIC: COSV104374810;