rs28566771

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000549.5(TSHB):​c.163-112C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

TSHB
NM_000549.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.509
Variant links:
Genes affected
TSHB (HGNC:12372): (thyroid stimulating hormone subunit beta) The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. Thyroid stimulating hormone functions in the control of thyroid structure and metabolism. The protein encoded by this gene is the beta subunit of thyroid stimulating hormone. Mutations in this gene are associated with congenital central and secondary hypothyroidism and Hashimoto's thyroiditis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSHBNM_000549.5 linkc.163-112C>A intron_variant Intron 2 of 2 ENST00000256592.3 NP_000540.2 P01222-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSHBENST00000256592.3 linkc.163-112C>A intron_variant Intron 2 of 2 5 NM_000549.5 ENSP00000256592.1 P01222-1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151818
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
52
AN:
1309410
Hom.:
0
Cov.:
20
AF XY:
0.0000349
AC XY:
23
AN XY:
658768
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000435
Gnomad4 OTH exome
AF:
0.000144
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151818
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74148
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
2.2
DANN
Benign
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs28566771; hg19: chr1-115576482; API