7-117170983-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001369598.1(ST7):c.1078+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,566,746 control chromosomes in the GnomAD database, including 37,147 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (7035 hom., cov: 31)
  • Exomes 𝑓: 0.20 (30112 hom.)
• Consequence: ST7 NM_001369598.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002399
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.116

Genes affected

ST7 (HGNC:11351): (suppression of tumorigenicity 7) The gene for this product maps to a region on chromosome 7 identified as an autism-susceptibility locus. Mutation screening of the entire coding region in autistic individuals failed to identify phenotype-specific variants, suggesting that coding mutations for this gene are unlikely to be involved in the etiology of autism. The function of this gene product has not been determined. Transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-117170983-T-C is Benign according to our data. Variant chr7-117170983-T-C is described in ClinVar as [Benign]. Clinvar id is 3055413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ST7	NM_001369598.1	c.1078+7T>C		splice_region_variant, intron_variant		ENST00000323984.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ST7	ENST00000323984.8	c.1078+7T>C		splice_region_variant, intron_variant		5	NM_001369598.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42022 AN: 151828 Hom.: 7010 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.258

GnomAD3 exomes AF: 0.219 AC: 52460 AN: 239194 Hom.: 6508 AF XY: 0.211 AC XY: 27274 AN XY: 129372

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.199 AC: 282176 AN: 1414800 Hom.: 30112 Cov.: 22 AF XY: 0.197 AC XY: 139269 AN XY: 705262

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.277 AC: 42099 AN: 151946 Hom.: 7035 Cov.: 31 AF XY: 0.272 AC XY: 20178 AN XY: 74250

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.260

Alfa AF: 0.209 Hom.: 7457

Bravo AF: 0.289

Asia WGS AF: 0.216 AC: 754 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ST7-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.1
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.0060
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: rs193562; hg19: chr7-116811037; COSMIC: COSV55385555; COSMIC: COSV55385555;