rs1017141

Positions:

• chr14-81103334-G-A
• chr14-81103334-G-C
• chr14-81103334-G-T

Variant summary

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

The NM_000369.5(TSHR):​c.615-5041G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 985,262 control chromosomes in the GnomAD database, including 333,302 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 0.84 (54223 hom., cov: 33)
  • Exomes 𝑓: 0.82 (279079 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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 (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.615-5041G>A		intron_variant		ENST00000298171.7
LOC101928462	XR_001751022.2	n.488-3808C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.615-5041G>A		intron_variant		1	NM_000369.5	P1
	ENST00000646052.2	n.511-3808C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128047 AN: 152118 Hom.: 54182 Cov.: 33

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.818 AC: 681707 AN: 833026 Hom.: 279079 Cov.: 33 AF XY: 0.818 AC XY: 314717 AN XY: 384680

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.737

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.846

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.816

Gnomad4 OTH exome AF: 0.814

GnomAD4 genome AF: 0.842 AC: 128141 AN: 152236 Hom.: 54223 Cov.: 33 AF XY: 0.839 AC XY: 62491 AN XY: 74444

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.819

Alfa AF: 0.824 Hom.: 67945

Bravo AF: 0.836

Asia WGS AF: 0.775 AC: 2692 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	1.1
DANN	Benign	0.36

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: rs1017141; hg19: chr14-81569678;