1-46177421-A-G

Variant summary

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

The NM_005727.4(TSPAN1):c.-142+2012A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,976 control chromosomes in the GnomAD database, including 4,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4601 hom., cov: 31)
• Consequence: TSPAN1 NM_005727.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53

Genes affected

TSPAN1 (HGNC:20657): (tetraspanin 1) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 1-46177421-A-G is Benign according to our data. Variant chr1-46177421-A-G is described in ClinVar as [Benign]. Clinvar id is 1281508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN1	NM_005727.4	c.-142+2012A>G		intron_variant		ENST00000372003.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN1	ENST00000372003.6	c.-142+2012A>G		intron_variant		1	NM_005727.4	P1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34425 AN: 151858 Hom.: 4574 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34514 AN: 151976 Hom.: 4601 Cov.: 31 AF XY: 0.235 AC XY: 17425 AN XY: 74282

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.210

Alfa AF: 0.188 Hom.: 414

Bravo AF: 0.230

Asia WGS AF: 0.425 AC: 1476 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 11, 2019

This variant is associated with the following publications: (PMID: 29802999) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.33
Dann	Benign	0.37

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: rs7536272; hg19: chr1-46643093;