chr14-80981938-C-G

Position:

• chr14-80981938-C-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+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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+26088C>G		intron_variant		ENST00000298171.7	NP_000360.2
TSHR	NM_001142626.3	c.170+26088C>G		intron_variant			NP_001136098.1
TSHR	NM_001018036.3	c.170+26088C>G		intron_variant			NP_001018046.1
GPRASP3P1		n.80981938C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.170+26088C>G		intron_variant		1	NM_000369.5	ENSP00000298171.2

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

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.494

Gnomad4 OTH exome AF: 0.510

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.492

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.032
DANN	Benign	0.37

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: rs3783950; hg19: chr14-81448282; COSMIC: COSV53321850; COSMIC: COSV53321850;