chr12-57749071-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005981.5(TSPAN31):c.*1781C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,346,344 control chromosomes in the GnomAD database, including 81,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6737 hom., cov: 32)

Exomes 𝑓: 0.34 ( 74845 hom. )

Consequence

TSPAN31
NM_005981.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.205

Publications

20 publications found

Variant links:

Genes affected

TSPAN31 (HGNC:10539): (tetraspanin 31) 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 thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

TSPAN31 links:

CDK4 (HGNC:1773): (cyclin dependent kinase 4) The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]

CDK4 Gene-Disease associations (from GenCC):

melanoma, cutaneous malignant, susceptibility to, 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
malignant pancreatic neoplasm
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

CDK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-57749071-C-A is Benign according to our data. Variant chr12-57749071-C-A is described in ClinVar as Benign. ClinVar VariationId is 1182049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005981.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSPAN31	NM_005981.5	MANE Select	c.*1781C>A	3_prime_UTR	Exon 6 of 6	NP_005972.1	Q12999
CDK4	NM_000075.4	MANE Select	c.819+111G>T	intron	N/A	NP_000066.1	P11802-1
TSPAN31	NM_001330169.2		c.*1781C>A	3_prime_UTR	Exon 6 of 6	NP_001317098.1	B4DFJ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSPAN31	ENST00000257910.8	TSL:1 MANE Select	c.*1781C>A	3_prime_UTR	Exon 6 of 6	ENSP00000257910.3	Q12999
TSPAN31	ENST00000547992.5	TSL:1	c.*1781C>A	3_prime_UTR	Exon 4 of 4	ENSP00000448209.1	F8VS78
CDK4	ENST00000257904.11	TSL:1 MANE Select	c.819+111G>T	intron	N/A	ENSP00000257904.5	P11802-1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40291

AN:

152066

Hom.:

6734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.339

AC:

405229

AN:

1194160

Hom.:

74845

Cov.:

AF XY:

0.345

AC XY:

208953

AN XY:

606228

show subpopulations

African (AFR)

AF:

0.0729

AC:

2066

AN:

28342

American (AMR)

AF:

0.334

AC:

14740

AN:

44126

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

7024

AN:

24342

East Asian (EAS)

AF:

0.707

AC:

27212

AN:

38474

South Asian (SAS)

AF:

0.487

AC:

39147

AN:

80422

European-Finnish (FIN)

AF:

0.353

AC:

18775

AN:

53202

Middle Eastern (MID)

AF:

0.191

AC:

1005

AN:

5252

European-Non Finnish (NFE)

AF:

0.321

AC:

278760

AN:

868486

Other (OTH)

AF:

0.320

AC:

16500

AN:

51514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13549

27098

40646

54195

67744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8266

16532

24798

33064

41330

<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:

0.265

AC:

40297

AN:

152184

Hom.:

6737

Cov.:

AF XY:

0.273

AC XY:

20302

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0818

AC:

3398

AN:

41544

American (AMR)

AF:

0.256

AC:

3919

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1004

AN:

3470

East Asian (EAS)

AF:

0.655

AC:

3381

AN:

5158

South Asian (SAS)

AF:

0.491

AC:

2368

AN:

4818

European-Finnish (FIN)

AF:

0.373

AC:

3953

AN:

10592

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21384

AN:

67996

Other (OTH)

AF:

0.235

AC:

496

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1449

2899

4348

5798

7247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.279

Hom.:

835

Bravo

AF:

0.247

Asia WGS

AF:

0.511

AC:

1775

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.6

(source)

DANN

Benign

0.60

PhyloP100

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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