rs116938497

chr7-120815720-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012338.4(TSPAN12):c.360+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 1,610,184 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (103 hom.)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.342

Genes affected

TSPAN12 (HGNC:21641): (tetraspanin 12) 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-120815720-T-C is Benign according to our data. Variant chr7-120815720-T-C is described in ClinVar as [Benign]. Clinvar id is 358763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00761 (1160/152344) while in subpopulation NFE AF= 0.0114 (776/68034). AF 95% confidence interval is 0.0107. There are 6 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN12	NM_012338.4	c.360+9A>G		intron_variant		ENST00000222747.8
TSPAN12	XM_005250239.4	c.360+9A>G		intron_variant
TSPAN12	XM_047420095.1	c.360+9A>G		intron_variant
TSPAN12	XM_047420096.1	c.286-5150A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN12	ENST00000222747.8	c.360+9A>G		intron_variant		1	NM_012338.4	P1

Frequencies

GnomAD3 genomes AF: 0.00762 AC: 1160 AN: 152226 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00777 AC: 1927 AN: 248058 Hom.: 11 AF XY: 0.00795 AC XY: 1066 AN XY: 134166

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.00850

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00192

Gnomad FIN exome AF: 0.000852

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.00926

GnomAD4 exome AF: 0.00992 AC: 14458 AN: 1457840 Hom.: 103 Cov.: 30 AF XY: 0.00980 AC XY: 7109 AN XY: 725246

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00864

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00200

Gnomad4 FIN exome AF: 0.00145

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.0100

GnomAD4 genome AF: 0.00761 AC: 1160 AN: 152344 Hom.: 6 Cov.: 32 AF XY: 0.00706 AC XY: 526 AN XY: 74496

Gnomad4 AFR AF: 0.00216

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0100 Hom.: 2

Bravo AF: 0.00848

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Exudative vitreoretinopathy 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	14
Dann	Benign	0.84

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: rs116938497; hg19: chr7-120455774;