chr14-80982038-T-G

Position:

• chr14-80982038-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.170+26188T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 415,284 control chromosomes in the GnomAD database, including 51,239 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 0.48 (17848 hom., cov: 32)
  • Exomes 𝑓: 0.50 (33391 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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]

GPRASP3P1 (HGNC:51373): (GPRASP3 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+26188T>G		intron_variant		ENST00000298171.7	NP_000360.2
TSHR	NM_001018036.3	c.170+26188T>G		intron_variant			NP_001018046.1
TSHR	NM_001142626.3	c.170+26188T>G		intron_variant			NP_001136098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.170+26188T>G		intron_variant		1	NM_000369.5	ENSP00000298171	P1
GPRASP3P1	ENST00000553845.1	n.51T>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72904 AN: 151536 Hom.: 17819 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.498 AC: 131159 AN: 263630 Hom.: 33391 Cov.: 0 AF XY: 0.495 AC XY: 70627 AN XY: 142800

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.657

Gnomad4 SAS exome AF: 0.510

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.498

GnomAD4 genome AF: 0.481 AC: 72989 AN: 151654 Hom.: 17848 Cov.: 32 AF XY: 0.481 AC XY: 35621 AN XY: 74100

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.478

Alfa AF: 0.480 Hom.: 38052

Bravo AF: 0.487

Asia WGS AF: 0.578 AC: 2010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.1
DANN	Benign	0.20

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: rs3783949; hg19: chr14-81448382; COSMIC: COSV53321857;