chr14-81108343-T-TTC

Position:

• chr14-81108343-T-TTC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000369.5(TSHR):​c.615-20_615-19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0087 in 1,268,172 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0099 (2 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.615-20_615-19dup		intron_variant		ENST00000298171.7	NP_000360.2
LOC101928462	XR_001751022.2	n.488-8818_488-8817insGA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.615-20_615-19dup		intron_variant		1	NM_000369.5	ENSP00000298171	P1
	ENST00000646052.2	n.511-8818_511-8817insGA		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000730 AC: 11 AN: 150694 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000444

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00578 AC: 1117 AN: 193136 Hom.: 1 AF XY: 0.00593 AC XY: 613 AN XY: 103378

Gnomad AFR exome AF: 0.00262

Gnomad AMR exome AF: 0.00826

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.000700

Gnomad SAS exome AF: 0.0134

Gnomad FIN exome AF: 0.00476

Gnomad NFE exome AF: 0.00449

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00987 AC: 11024 AN: 1117362 Hom.: 2 Cov.: 24 AF XY: 0.00948 AC XY: 5291 AN XY: 558100

Gnomad4 AFR exome AF: 0.00843

Gnomad4 AMR exome AF: 0.00604

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.00923

Gnomad4 FIN exome AF: 0.00475

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.00876

GnomAD4 genome AF: 0.0000729 AC: 11 AN: 150810 Hom.: 0 Cov.: 0 AF XY: 0.0000543 AC XY: 4 AN XY: 73630

Gnomad4 AFR AF: 0.0000973

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000195

Gnomad4 NFE AF: 0.0000444

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3837640; hg19: chr14-81574687;