chr12-71125393-G-A

Variant names:

• chr12-71125393-G-A
• rs11178636
• NM_004616.3:c.661-6C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004616.3(TSPAN8):​c.661-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,608,940 control chromosomes in the GnomAD database, including 173 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 0.014 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (138 hom.)
• Consequence: TSPAN8 NM_004616.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002133
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.15
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 12-71125393-G-A is Benign according to our data. Variant chr12-71125393-G-A is described in ClinVar as Benign. ClinVar VariationId is 779949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0145 (2205/152172) while in subpopulation EAS AF = 0.0524 (271/5176). AF 95% confidence interval is 0.0472. There are 35 homozygotes in GnomAd4. There are 1085 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	NM_004616.3	MANE Select	c.661-6C>T		splice_region intron	N/A	NP_004607.1	P19075
	TSPAN8	NM_001369760.1		c.661-6C>T		splice_region intron	N/A	NP_001356689.1	P19075

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSPAN8	ENST00000247829.8	TSL:1 MANE Select	c.661-6C>T		splice_region intron	N/A	ENSP00000247829.3	P19075
	TSPAN8	ENST00000393330.6	TSL:1	c.661-6C>T		splice_region intron	N/A	ENSP00000377003.2	P19075
	TSPAN8	ENST00000546561.2	TSL:1	c.661-6C>T		splice_region intron	N/A	ENSP00000447160.1	P19075

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2197 AN: 152054 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00807 AC: 1989 AN: 246476 AF XY: 0.00732

Gnomad AFR exome AF: 0.0408

Gnomad AMR exome AF: 0.00288

Gnomad ASJ exome AF: 0.00520

Gnomad EAS exome AF: 0.0443

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000250

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.00361 AC: 5265 AN: 1456768 Hom.: 138 Cov.: 30 AF XY: 0.00364 AC XY: 2641 AN XY: 724680

African (AFR) AF: 0.0443 AC: 1468 AN: 33172

American (AMR) AF: 0.00289 AC: 126 AN: 43598

Ashkenazi Jewish (ASJ) AF: 0.00648 AC: 168 AN: 25924

East Asian (EAS) AF: 0.0519 AC: 2056 AN: 39648

South Asian (SAS) AF: 0.0102 AC: 866 AN: 85172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5718

European-Non Finnish (NFE) AF: 0.000122 AC: 135 AN: 1110036

Other (OTH) AF: 0.00725 AC: 436 AN: 60152

GnomAD4 genome AF: 0.0145 AC: 2205 AN: 152172 Hom.: 35 Cov.: 32 AF XY: 0.0146 AC XY: 1085 AN XY: 74404

African (AFR) AF: 0.0414 AC: 1717 AN: 41516

American (AMR) AF: 0.00471 AC: 72 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.0524 AC: 271 AN: 5176

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68012

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00640 Hom.: 8

Bravo AF: 0.0160

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.8
DANN	Benign	0.53
PhyloP100		2.1
Mutation Taster		=95/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs11178636; hg19: chr12-71519173; COSMIC: COSV56080120;