rs6466759

chr7-120829636-T-Achr7-120829636-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012338.4(TSPAN12):c.285+9141A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,970 control chromosomes in the GnomAD database, including 14,009 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (14009 hom., cov: 32)
• Consequence: TSPAN12 NM_012338.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN12	NM_012338.4	c.285+9141A>T		intron_variant		ENST00000222747.8
TSPAN12	XM_005250239.4	c.285+9141A>T		intron_variant
TSPAN12	XM_047420095.1	c.285+9141A>T		intron_variant
TSPAN12	XM_047420096.1	c.285+9141A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN12	ENST00000222747.8	c.285+9141A>T		intron_variant		1	NM_012338.4	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59296 AN: 151852 Hom.: 13965 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.391 AC: 59412 AN: 151970 Hom.: 14009 Cov.: 32 AF XY: 0.394 AC XY: 29244 AN XY: 74276

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.349

Alfa AF: 0.201 Hom.: 457

Bravo AF: 0.404

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.14
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6466759; hg19: chr7-120469690;