NM_000369.5:c.170+26188T>G

Variant names:

• chr14-80982038-T-G
• rs3783949
• NM_000369.5:c.170+26188T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+26188T>G		intron_variant	Intron 1 of 9	ENST00000298171.7	NP_000360.2
GPRASP3P1		n.80982038T>G		intragenic_variant
TSHR	NM_001142626.3	c.170+26188T>G		intron_variant	Intron 1 of 8		NP_001136098.1
TSHR	NM_001018036.3	c.170+26188T>G		intron_variant	Intron 1 of 8		NP_001018046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.170+26188T>G		intron_variant	Intron 1 of 9	1	NM_000369.5	ENSP00000298171.2

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

African (AFR) AF: 0.459 AC: 3531 AN: 7690

American (AMR) AF: 0.599 AC: 11578 AN: 19342

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 3453 AN: 6394

East Asian (EAS) AF: 0.657 AC: 9571 AN: 14568

South Asian (SAS) AF: 0.510 AC: 13316 AN: 26090

European-Finnish (FIN) AF: 0.472 AC: 13191 AN: 27962

Middle Eastern (MID) AF: 0.385 AC: 574 AN: 1492

European-Non Finnish (NFE) AF: 0.472 AC: 69186 AN: 146532

Other (OTH) AF: 0.498 AC: 6759 AN: 13560

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

African (AFR) AF: 0.452 AC: 18686 AN: 41338

American (AMR) AF: 0.538 AC: 8207 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3247 AN: 5160

South Asian (SAS) AF: 0.518 AC: 2486 AN: 4802

European-Finnish (FIN) AF: 0.460 AC: 4821 AN: 10488

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 31992 AN: 67830

Other (OTH) AF: 0.478 AC: 1009 AN: 2110

Alfa AF: 0.479 Hom.: 51019

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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