Genetic Variant ENST00000426643.1: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HCG23	NR_044996.1 link	n.373-115C>T	intron_variant	Intron 2 of 2
TSBP1-AS1	NR_136245.1 link	n.303-12120C>T	intron_variant	Intron 2 of 3
BTNL2	NM_001304561.2 link	c.*62G>A	downstream_gene_variant		ENST00000454136.8	NP_001291490.1	Q9UIR0F8WBA1A0PJV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL2	ENST00000454136.8 link	c.*62G>A		downstream_gene_variant		5	NM_001304561.2	ENSP00000390613.3		F8WBA1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over