rs123598

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004656.4(BAP1):c.*444C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 292,396 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 143 hom., cov: 33)

Exomes 𝑓: 0.040 ( 141 hom. )

Consequence

BAP1
NM_004656.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.271

Publications

15 publications found

Variant links:

Genes affected

BAP1 (HGNC:950): (BRCA1 associated protein 1) This gene belongs to the ubiquitin C-terminal hydrolase subfamily of deubiquitinating enzymes that are involved in the removal of ubiquitin from proteins. The encoded enzyme binds to the breast cancer type 1 susceptibility protein (BRCA1) via the RING finger domain of the latter and acts as a tumor suppressor. In addition, the enzyme may be involved in regulation of transcription, regulation of cell cycle and growth, response to DNA damage and chromatin dynamics. Germline mutations in this gene may be associated with tumor predisposition syndrome (TPDS), which involves increased risk of cancers including malignant mesothelioma, uveal melanoma and cutaneous melanoma. [provided by RefSeq, May 2013]

BAP1 Gene-Disease associations (from GenCC):

BAP1-related tumor predisposition syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Kury-Isidor syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
renal cell carcinoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

BAP1 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=-0.82).

BP6

Variant 3-52401844-G-A is Benign according to our data. Variant chr3-52401844-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 346111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0361 (5493/152308) while in subpopulation NFE AF = 0.0497 (3377/68012). AF 95% confidence interval is 0.0483. There are 143 homozygotes in GnomAd4. There are 2529 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 5493 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004656.4. 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
	BAP1	NM_004656.4	MANE Select	c.*444C>T		3_prime_UTR	Exon 17 of 17	NP_004647.1	Q92560
	BAP1	NM_001410772.1		c.*444C>T		3_prime_UTR	Exon 17 of 17	NP_001397701.1	F8W6N3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BAP1	ENST00000460680.6	TSL:1 MANE Select	c.*444C>T	3_prime_UTR	Exon 17 of 17	ENSP00000417132.1	Q92560
BAP1	ENST00000478368.1	TSL:1	c.*444C>T	3_prime_UTR	Exon 5 of 5	ENSP00000420647.1	H0Y8E8
BAP1	ENST00000469613.5	TSL:1	c.*444C>T	3_prime_UTR	Exon 5 of 5	ENSP00000418320.1	H7C4V7

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5492

AN:

152190

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0217

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0421

GnomAD4 exome

AF:

0.0402

AC:

5638

AN:

140088

Hom.:

141

Cov.:

AF XY:

0.0396

AC XY:

2709

AN XY:

68426

show subpopulations

African (AFR)

AF:

0.0150

AC:

AN:

5648

American (AMR)

AF:

0.0435

AC:

271

AN:

6228

Ashkenazi Jewish (ASJ)

AF:

0.0310

AC:

202

AN:

6514

East Asian (EAS)

AF:

0.0150

AC:

220

AN:

14626

South Asian (SAS)

AF:

0.0157

AC:

150

AN:

9556

European-Finnish (FIN)

AF:

0.0261

AC:

AN:

2490

Middle Eastern (MID)

AF:

0.0277

AC:

AN:

686

European-Non Finnish (NFE)

AF:

0.0489

AC:

4135

AN:

84606

Other (OTH)

AF:

0.0504

AC:

491

AN:

9734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

311

623

934

1246

1557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0361

AC:

5493

AN:

152308

Hom.:

143

Cov.:

AF XY:

0.0340

AC XY:

2529

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0138

AC:

575

AN:

41564

American (AMR)

AF:

0.0470

AC:

719

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3472

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5184

South Asian (SAS)

AF:

0.0213

AC:

103

AN:

4826

European-Finnish (FIN)

AF:

0.0301

AC:

320

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0497

AC:

3377

AN:

68012

Other (OTH)

AF:

0.0440

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

264

527

791

1054

1318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0477

Hom.:

252

Bravo

AF:

0.0371

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

BAP1-related tumor predisposition syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.80

(source)

DANN

Benign

0.27

PhyloP100

-0.27

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(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