Genetic Variant TSBP1-AS1:n.373-115C>T (chr6-32393334-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000426643.1(TSBP1-AS1):n.373-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,492 control chromosomes in the GnomAD database, including 12,011 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 11973 hom., cov: 32)

Exomes 𝑓: 0.41 ( 38 hom. )

Consequence

TSBP1-AS1
ENST00000426643.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.817

Publications

47 publications found

Variant links:

COSMIC-nc: COSV66631911

Genes affected

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

TSBP1-AS1 links:

HCG23 (HGNC:19713): (HLA complex group 23)

HCG23 links:

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

BTNL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426643.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HCG23	NR_044996.1		n.373-115C>T	intron	N/A
TSBP1-AS1	NR_136245.1		n.303-12120C>T	intron	N/A
BTNL2	NM_001304561.2	MANE Select	c.*62G>A	downstream_gene	N/A	NP_001291490.1	Q9UIR0-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
TSBP1-AS1	ENST00000426643.1	TSL:3	n.373-115C>T	intron	N/A
TSBP1-AS1	ENST00000642577.1		n.708+2581C>T	intron	N/A
TSBP1-AS1	ENST00000645134.1		n.627+2581C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60079

AN:

151896

Hom.:

11973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.394

GnomAD4 exome

AF:

0.408

AC:

195

AN:

478

Hom.:

AF XY:

0.433

AC XY:

129

AN XY:

298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.425

AC:

181

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.239

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.395

AC:

60098

AN:

152014

Hom.:

11973

Cov.:

AF XY:

0.397

AC XY:

29458

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.331

AC:

13729

AN:

41448

American (AMR)

AF:

0.434

AC:

6633

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1333

AN:

3472

East Asian (EAS)

AF:

0.301

AC:

1558

AN:

5172

South Asian (SAS)

AF:

0.417

AC:

2003

AN:

4808

European-Finnish (FIN)

AF:

0.456

AC:

4806

AN:

10532

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28690

AN:

67982

Other (OTH)

AF:

0.387

AC:

818

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1866

3731

5597

7462

9328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.410

Hom.:

37426

Bravo

AF:

0.396

Asia WGS

AF:

0.318

AC:

1107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.2

(source)

DANN

Benign

0.21

PhyloP100

-0.82

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over