chr14-80984708-C-T

Variant names:

• chr14-80984708-C-T
• rs12101255
• NM_000369.5:c.170+28858C>T

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+28858C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,040 control chromosomes in the GnomAD database, including 11,242 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 0.38 (11242 hom., cov: 32)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 25 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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+28858C>T		intron	N/A	NP_000360.2	P16473-1
	TSHR	NM_001142626.3		c.170+28858C>T		intron	N/A	NP_001136098.1	P16473-3
	TSHR	NM_001018036.3		c.170+28858C>T		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+28858C>T		intron	N/A	ENSP00000298171.2	P16473-1
	TSHR	ENST00000554435.1	TSL:1	c.170+28858C>T		intron	N/A	ENSP00000450549.1	P16473-3
	TSHR	ENST00000342443.10	TSL:1	c.170+28858C>T		intron	N/A	ENSP00000340113.6	P16473-2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57147 AN: 151922 Hom.: 11214 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57232 AN: 152040 Hom.: 11242 Cov.: 32 AF XY: 0.373 AC XY: 27746 AN XY: 74324

African (AFR) AF: 0.394 AC: 16327 AN: 41438

American (AMR) AF: 0.470 AC: 7185 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3466

East Asian (EAS) AF: 0.618 AC: 3190 AN: 5164

South Asian (SAS) AF: 0.294 AC: 1418 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2983 AN: 10580

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23455 AN: 67970

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.372 Hom.: 1819

Bravo AF: 0.396

Asia WGS AF: 0.485 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.5
DANN	Benign	0.49
PhyloP100		-0.67
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: rs12101255; hg19: chr14-81451052;