rs12885526

chr14-81108085-G-Achr14-81108085-G-T

Variant summary

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

The NM_000369.5(TSHR):c.615-290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,804 control chromosomes in the GnomAD database, including 30,080 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 0.62 (30080 hom., cov: 31)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSHR	NM_000369.5	c.615-290G>A		intron_variant		ENST00000298171.7
LOC101928462	XR_001751022.2	n.488-8559C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSHR	ENST00000298171.7	c.615-290G>A		intron_variant		1	NM_000369.5	P1
	ENST00000646052.2	n.511-8559C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94814 AN: 151688 Hom.: 30070 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.625 AC: 94873 AN: 151804 Hom.: 30080 Cov.: 31 AF XY: 0.623 AC XY: 46237 AN XY: 74178

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.646

Alfa AF: 0.633 Hom.: 3805

Bravo AF: 0.617

Asia WGS AF: 0.594 AC: 2063 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.56
Dann	Benign	0.59

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: rs12885526; hg19: chr14-81574429; COSMIC: COSV53332933; COSMIC: COSV53332933;