chr7-129203328-C-T

Position:

• chr7-129203328-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005631.5(SMO):​c.332-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,327,394 control chromosomes in the GnomAD database, including 169,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18516 hom., cov: 33)
  • Exomes 𝑓: 0.50 (151054 hom.)
• Consequence: SMO NM_005631.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-129203328-C-T is Benign according to our data. Variant chr7-129203328-C-T is described in ClinVar as [Benign]. Clinvar id is 1244213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5	c.332-56C>T		intron_variant		ENST00000249373.8
SMO	XM_047420759.1	c.-59-56C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8	c.332-56C>T		intron_variant		1	NM_005631.5	P1
SMO	ENST00000655644.1	c.*196-56C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74764 AN: 152004 Hom.: 18493 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.504 AC: 592524 AN: 1175272 Hom.: 151054 AF XY: 0.503 AC XY: 294863 AN XY: 585798

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.520

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.492 AC: 74829 AN: 152122 Hom.: 18516 Cov.: 33 AF XY: 0.486 AC XY: 36123 AN XY: 74342

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.525

Alfa AF: 0.521 Hom.: 20377

Bravo AF: 0.493

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2566871; hg19: chr7-128843169; COSMIC: COSV50824292; COSMIC: COSV50824292;