12-71139714-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_004616.3(TSPAN8):c.258G>A(p.Leu86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,310 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (84 hom.)
• Consequence: TSPAN8 NM_004616.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.132

Genes affected

TSPAN8 (HGNC:11855): (tetraspanin 8) 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. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-71139714-C-T is Benign according to our data. Variant chr12-71139714-C-T is described in ClinVar as [Benign]. Clinvar id is 779950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.132 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00263 (400/152268) while in subpopulation EAS AF= 0.0494 (255/5158). AF 95% confidence interval is 0.0445. There are 8 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSPAN8	NM_004616.3	c.258G>A	p.Leu86=	synonymous_variant	4/9	ENST00000247829.8
TSPAN8	NM_001369760.1	c.258G>A	p.Leu86=	synonymous_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSPAN8	ENST00000247829.8	c.258G>A	p.Leu86=	synonymous_variant	4/9	1	NM_004616.3	P1
TSPAN8	ENST00000393330.6	c.258G>A	p.Leu86=	synonymous_variant	7/12	1		P1
TSPAN8	ENST00000546561.2	c.258G>A	p.Leu86=	synonymous_variant	3/8	1		P1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152150 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00478 AC: 1196 AN: 250336 Hom.: 22 AF XY: 0.00487 AC XY: 659 AN XY: 135308

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00550

Gnomad EAS exome AF: 0.0414

Gnomad SAS exome AF: 0.00942

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00227 AC: 3310 AN: 1461042 Hom.: 84 Cov.: 30 AF XY: 0.00249 AC XY: 1807 AN XY: 726836

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000851

Gnomad4 ASJ exome AF: 0.00652

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.00902

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000819

Gnomad4 OTH exome AF: 0.00424

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152268 Hom.: 8 Cov.: 33 AF XY: 0.00290 AC XY: 216 AN XY: 74458

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.0494

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000835 Hom.: 1

Bravo AF: 0.00232

Asia WGS AF: 0.0260 AC: 89 AN: 3478

EpiCase AF: 0.000328

EpiControl AF: 0.00

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

Invitae

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	1.4
Dann	Benign	0.67

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: rs117090819; hg19: chr12-71533494; COSMIC: COSV56078238; COSMIC: COSV56078238;