rs917986

Positions:

• chr14-81004311-C-A
• chr14-81004311-C-G

Variant summary

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

The NM_000369.5(TSHR):​c.170+48461C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,060 control chromosomes in the GnomAD database, including 32,296 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 0.62 (32296 hom., cov: 32)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.170+48461C>A		intron_variant		ENST00000298171.7
TSHR	NM_001018036.3	c.170+48461C>A		intron_variant
TSHR	NM_001142626.3	c.170+48461C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.170+48461C>A		intron_variant		1	NM_000369.5	P1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94890 AN: 151942 Hom.: 32287 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.624 AC: 94929 AN: 152060 Hom.: 32296 Cov.: 32 AF XY: 0.629 AC XY: 46775 AN XY: 74326

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.641

Alfa AF: 0.723 Hom.: 80735

Bravo AF: 0.602

Asia WGS AF: 0.652 AC: 2272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.62

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: rs917986; hg19: chr14-81470655;