chr14-80981938-C-G

Variant names:

• chr14-80981938-C-G
• rs3783950
• NM_000369.5:c.170+26088C>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+26088C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 276,362 control chromosomes in the GnomAD database, including 35,881 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 0.49 (18859 hom., cov: 32)
  • Exomes 𝑓: 0.52 (17022 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000369.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHR	NM_000369.5	MANE Select	c.170+26088C>G		intron	N/A	NP_000360.2	P16473-1
	TSHR	NM_001142626.3		c.170+26088C>G		intron	N/A	NP_001136098.1	P16473-3
	TSHR	NM_001018036.3		c.170+26088C>G		intron	N/A	NP_001018046.1	P16473-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHR	ENST00000298171.7	TSL:1 MANE Select	c.170+26088C>G		intron	N/A	ENSP00000298171.2	P16473-1
	TSHR	ENST00000554435.1	TSL:1	c.170+26088C>G		intron	N/A	ENSP00000450549.1	P16473-3
	TSHR	ENST00000342443.10	TSL:1	c.170+26088C>G		intron	N/A	ENSP00000340113.6	P16473-2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75026 AN: 151892 Hom.: 18827 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.490

GnomAD4 exome AF: 0.518 AC: 64451 AN: 124352 Hom.: 17022 Cov.: 0 AF XY: 0.514 AC XY: 34459 AN XY: 67020

African (AFR) AF: 0.496 AC: 1786 AN: 3600

American (AMR) AF: 0.624 AC: 6226 AN: 9982

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 1531 AN: 2642

East Asian (EAS) AF: 0.667 AC: 5289 AN: 7932

South Asian (SAS) AF: 0.523 AC: 5176 AN: 9888

European-Finnish (FIN) AF: 0.482 AC: 10059 AN: 20872

Middle Eastern (MID) AF: 0.488 AC: 167 AN: 342

European-Non Finnish (NFE) AF: 0.494 AC: 31152 AN: 63082

Other (OTH) AF: 0.510 AC: 3065 AN: 6012

GnomAD4 genome AF: 0.494 AC: 75117 AN: 152010 Hom.: 18859 Cov.: 32 AF XY: 0.493 AC XY: 36600 AN XY: 74302

African (AFR) AF: 0.472 AC: 19575 AN: 41452

American (AMR) AF: 0.544 AC: 8315 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1985 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3257 AN: 5174

South Asian (SAS) AF: 0.521 AC: 2510 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4885 AN: 10550

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32918 AN: 67954

Other (OTH) AF: 0.492 AC: 1038 AN: 2108

Alfa AF: 0.318 Hom.: 755

Bravo AF: 0.502

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.032
DANN	Benign	0.37
PhyloP100		-1.9
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: rs3783950; hg19: chr14-81448282; COSMIC: COSV53321850; COSMIC: COSV53321850;