rs4903957

chr14-80982167-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000369.5(TSHR):c.170+26317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 571,004 control chromosomes in the GnomAD database, including 27,178 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 0.27 (6437 hom., cov: 32)
  • Exomes 𝑓: 0.31 (20741 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.170+26317G>A		intron_variant		ENST00000298171.7
TSHR	NM_001018036.3	c.170+26317G>A		intron_variant
TSHR	NM_001142626.3	c.170+26317G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.170+26317G>A		intron_variant		1	NM_000369.5	P1
GPRASP3P1	ENST00000553845.1	n.180G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40982 AN: 152002 Hom.: 6433 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.306 AC: 128219 AN: 418884 Hom.: 20741 Cov.: 4 AF XY: 0.306 AC XY: 69566 AN XY: 227218

Gnomad4 AFR exome AF: 0.0975

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.270 AC: 41002 AN: 152120 Hom.: 6437 Cov.: 32 AF XY: 0.269 AC XY: 19980 AN XY: 74356

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.283

Alfa AF: 0.288 Hom.: 1363

Bravo AF: 0.265

Asia WGS AF: 0.295 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.40

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: rs4903957; hg19: chr14-81448511; COSMIC: COSV53320302;