rs3783949

Variant names:

• chr14-80982038-T-A
• rs3783949
• NM_000369.5:c.170+26188T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-80982038-T-A
• chr14-80982038-T-C
• chr14-80982038-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000369.5(TSHR):​c.170+26188T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 264,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSHR	NM_000369.5	c.170+26188T>A		intron_variant	Intron 1 of 9	ENST00000298171.7	NP_000360.2
GPRASP3P1		n.80982038T>A		intragenic_variant
TSHR	NM_001142626.3	c.170+26188T>A		intron_variant	Intron 1 of 8		NP_001136098.1
TSHR	NM_001018036.3	c.170+26188T>A		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+26188T>A		intron_variant	Intron 1 of 9	1	NM_000369.5	ENSP00000298171.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000378 AC: 1 AN: 264598 Hom.: 0 Cov.: 0 AF XY: 0.00000698 AC XY: 1 AN XY: 143338

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7710

American (AMR) AF: 0.00 AC: 0 AN: 19398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6428

East Asian (EAS) AF: 0.00 AC: 0 AN: 14612

South Asian (SAS) AF: 0.00 AC: 0 AN: 26252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1500

European-Non Finnish (NFE) AF: 0.00000680 AC: 1 AN: 147086

Other (OTH) AF: 0.00 AC: 0 AN: 13608

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 51019

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.0
DANN	Benign	0.063
PhyloP100		-1.6

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: rs3783949; hg19: chr14-81448382;