rs179247

Variant names:

• chr14-80966202-A-G
• rs179247
• NM_000369.5:c.170+10352A>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+10352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,000 control chromosomes in the GnomAD database, including 14,194 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 0.41 (14194 hom., cov: 32)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 38 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]

TSHR Gene-Disease associations (from GenCC):

• familial gestational hyperthyroidism

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• hypothyroidism due to TSH receptor mutations

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• familial hyperthyroidism due to mutations in TSH receptor

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• athyreosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hypoplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+10352A>G		intron_variant	Intron 1 of 9	ENST00000298171.7	NP_000360.2
TSHR	NM_001142626.3	c.170+10352A>G		intron_variant	Intron 1 of 8		NP_001136098.1
TSHR	NM_001018036.3	c.170+10352A>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+10352A>G		intron_variant	Intron 1 of 9	1	NM_000369.5	ENSP00000298171.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61681 AN: 151882 Hom.: 14196 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.406 AC: 61693 AN: 152000 Hom.: 14194 Cov.: 32 AF XY: 0.413 AC XY: 30698 AN XY: 74284

African (AFR) AF: 0.188 AC: 7817 AN: 41474

American (AMR) AF: 0.396 AC: 6054 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1866 AN: 5164

South Asian (SAS) AF: 0.595 AC: 2868 AN: 4820

European-Finnish (FIN) AF: 0.581 AC: 6132 AN: 10552

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34061 AN: 67932

Other (OTH) AF: 0.412 AC: 870 AN: 2110

Alfa AF: 0.468 Hom.: 29021

Bravo AF: 0.375

Asia WGS AF: 0.420 AC: 1459 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		-0.22
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: rs179247; hg19: chr14-81432546;