chr1-115033094-A-G

Position:

• chr1-115033094-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000549.5(TSHB):​c.-1-268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,110 control chromosomes in the GnomAD database, including 5,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5380 hom., cov: 30)
• Consequence: TSHB NM_000549.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.348

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-115033094-A-G is Benign according to our data. Variant chr1-115033094-A-G is described in ClinVar as [Benign]. Clinvar id is 1289439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHB	NM_000549.5	c.-1-268A>G		intron_variant		ENST00000256592.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHB	ENST00000256592.3	c.-1-268A>G		intron_variant		5	NM_000549.5	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39497 AN: 150992 Hom.: 5369 Cov.: 30

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 39547 AN: 151110 Hom.: 5380 Cov.: 30 AF XY: 0.267 AC XY: 19688 AN XY: 73742

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.252

Alfa AF: 0.248 Hom.: 8400

Bravo AF: 0.262

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
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

Other links and lift over

dbSNP: rs11102875; hg19: chr1-115575715;