Variant 1-115033861-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000549.5(TSHB):c.163-112C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 1,458,986 control chromosomes in the GnomAD database, including 168,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16622 hom., cov: 32)

Exomes 𝑓: 0.48 ( 151884 hom. )

Consequence

TSHB
NM_000549.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

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]

TSHB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-115033861-C-G is Benign according to our data. Variant chr1-115033861-C-G is described in ClinVar as [Benign]. Clinvar id is 1268415.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHB	NM_000549.5 linkuse as main transcript	c.163-112C>G		intron_variant		ENST00000256592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHB	ENST00000256592.3 linkuse as main transcript	c.163-112C>G		intron_variant		5	NM_000549.5	P1	P01222-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70506

AN:

151738

Hom.:

16620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.479

AC:

626371

AN:

1307130

Hom.:

151884

Cov.:

AF XY:

0.477

AC XY:

313882

AN XY:

657700

show subpopulations

Gnomad4 AFR exome

AF:

0.440

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.465

AC:

70550

AN:

151856

Hom.:

16622

Cov.:

AF XY:

0.459

AC XY:

34057

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.539

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.480

Alfa

AF:

0.336

Hom.:

896

Bravo

AF:

0.467

Asia WGS

AF:

0.420

AC:

1461

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.3

DANN

Benign

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over