Genetic Variant TSBP1-AS1:n.227G>A (chr6-32390736-G-A) – 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.227G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,090 control chromosomes in the GnomAD database, including 39,385 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 0.72 ( 39385 hom., cov: 32)

Exomes 𝑓: 0.40 ( 0 hom. )

Consequence

TSBP1-AS1
ENST00000426643.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

Publications

76 publications found

Variant links:

Genes affected

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

TSBP1-AS1 links:

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

HCG23 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000426643.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.95).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCG23	NR_044996.1		n.227G>A		non_coding_transcript_exon	Exon 1 of 3
	TSBP1-AS1	NR_136245.1		n.303-14718G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
TSBP1-AS1	ENST00000426643.1	TSL:3	n.227G>A	non_coding_transcript_exon	Exon 1 of 3
TSBP1-AS1	ENST00000642577.1		n.691G>A	non_coding_transcript_exon	Exon 3 of 6
TSBP1-AS1	ENST00000644884.2		n.1391G>A	non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

109154

AN:

151962

Hom.:

39362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.772

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.691

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.755

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.723

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0206134), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.718

AC:

109224

AN:

152080

Hom.:

39385

Cov.:

AF XY:

0.717

AC XY:

53317

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.772

AC:

32007

AN:

41478

American (AMR)

AF:

0.691

AC:

10570

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2414

AN:

3472

East Asian (EAS)

AF:

0.734

AC:

3799

AN:

5174

South Asian (SAS)

AF:

0.710

AC:

3421

AN:

4816

European-Finnish (FIN)

AF:

0.755

AC:

7963

AN:

10552

Middle Eastern (MID)

AF:

0.558

AC:

163

AN:

292

European-Non Finnish (NFE)

AF:

0.686

AC:

46664

AN:

67986

Other (OTH)

AF:

0.717

AC:

1514

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1572

3144

4716

6288

7860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.700

Hom.:

144935

Bravo

AF:

0.721

Asia WGS

AF:

0.720

AC:

2505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.5

(source)

DANN

Benign

0.52

PhyloP100

-0.57

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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