Genetic Variant TSPAN11:c.457-7C>A (chr12-30982525-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001370302.1(TSPAN11):c.457-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,600,616 control chromosomes in the GnomAD database, including 27 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0045 ( 27 hom. )

Consequence

TSPAN11
NM_001370302.1 splice_region, intron

Scores

Splicing: ADA: 0.001596

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.635

Publications

0 publications found

Variant links:

Genes affected

TSPAN11 (HGNC:30795): (tetraspanin 11) Predicted to be involved in cell migration. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TSPAN11 links:

TSPAN11-AS1 (HGNC:56687): (TSPAN11 antisense RNA 1)

TSPAN11-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 12-30982525-C-A is Benign according to our data. Variant chr12-30982525-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642815.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370302.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSPAN11	NM_001370302.1	MANE Select	c.457-7C>A	splice_region intron	N/A	NP_001357231.1	A1L157
TSPAN11	NM_001080509.3		c.457-7C>A	splice_region intron	N/A	NP_001073978.1	A1L157
TSPAN11	NM_001370301.1		c.427-7C>A	splice_region intron	N/A	NP_001357230.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSPAN11	ENST00000546076.6	TSL:2 MANE Select	c.457-7C>A	splice_region intron	N/A	ENSP00000437403.1	A1L157
TSPAN11	ENST00000261177.10	TSL:1	c.457-7C>A	splice_region intron	N/A	ENSP00000261177.9	A1L157
TSPAN11	ENST00000851526.1		c.457-7C>A	splice_region intron	N/A	ENSP00000521585.1

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00470

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00284

AC:

708

AN:

248876

AF XY:

0.00301

show subpopulations

Gnomad AFR exome

AF:

0.000810

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00344

Gnomad NFE exome

AF:

0.00417

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00452

AC:

6551

AN:

1448234

Hom.:

Cov.:

AF XY:

0.00456

AC XY:

3274

AN XY:

717512

show subpopulations

African (AFR)

AF:

0.000451

AC:

AN:

33266

American (AMR)

AF:

0.00117

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00185

AC:

AN:

25948

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39290

South Asian (SAS)

AF:

0.00253

AC:

217

AN:

85744

European-Finnish (FIN)

AF:

0.00449

AC:

236

AN:

52574

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00518

AC:

5708

AN:

1101568

Other (OTH)

AF:

0.00449

AC:

268

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

361

721

1082

1442

1803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152382

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41600

American (AMR)

AF:

0.00144

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00376

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00470

AC:

320

AN:

68034

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00240

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00397

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.046

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over