rs17111394

Positions:

• chr14-81056784-T-C
• chr14-81056784-T-G

Variant summary

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

The NM_000369.5(TSHR):​c.171-5364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,208 control chromosomes in the GnomAD database, including 1,591 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 0.13 (1591 hom., cov: 32)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.171-5364T>C		intron_variant		ENST00000298171.7	NP_000360.2
LOC101928462	XR_001751022.2	n.1068-2968A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.171-5364T>C		intron_variant		1	NM_000369.5	ENSP00000298171	P1
	ENST00000646052.2	n.1091-2968A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20051 AN: 152090 Hom.: 1593 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.132 AC: 20057 AN: 152208 Hom.: 1591 Cov.: 32 AF XY: 0.129 AC XY: 9589 AN XY: 74394

Gnomad4 AFR AF: 0.0526

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.122

Alfa AF: 0.170 Hom.: 3509

Bravo AF: 0.129

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.70

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: rs17111394; hg19: chr14-81523128;