14-80962220-T-C

Position:

• chr14-80962220-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000369.5(TSHR):​c.170+6370T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,128 control chromosomes in the GnomAD database, including 26,803 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 0.58 (26803 hom., cov: 33)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

Genes affected

TSHR (HGNC:12373): (thyroid stimulating hormone receptor) The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+6370T>C		intron_variant		ENST00000298171.7	NP_000360.2
TSHR	NM_001018036.3	c.170+6370T>C		intron_variant			NP_001018046.1
TSHR	NM_001142626.3	c.170+6370T>C		intron_variant			NP_001136098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.170+6370T>C		intron_variant		1	NM_000369.5	ENSP00000298171	P1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87679 AN: 152010 Hom.: 26785 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.577 AC: 87726 AN: 152128 Hom.: 26803 Cov.: 33 AF XY: 0.587 AC XY: 43651 AN XY: 74368

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.592

Alfa AF: 0.607 Hom.: 6774

Bravo AF: 0.552

Asia WGS AF: 0.674 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.76

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: rs179243; hg19: chr14-81428564;