14-81088273-A-G

Position:

• chr14-81088273-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000369.5(TSHR):​c.392+245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,294 control chromosomes in the GnomAD database, including 830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (830 hom., cov: 32)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-81088273-A-G is Benign according to our data. Variant chr14-81088273-A-G is described in ClinVar as [Benign]. Clinvar id is 1283819.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSHR	NM_000369.5	c.392+245A>G		intron_variant		ENST00000298171.7	NP_000360.2
LOC101928462	XR_001751022.2	n.882-621T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSHR	ENST00000298171.7	c.392+245A>G		intron_variant		1	NM_000369.5	ENSP00000298171	P1
	ENST00000646052.2	n.905-621T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14051 AN: 152176 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.0922 AC: 14049 AN: 152294 Hom.: 830 Cov.: 32 AF XY: 0.0928 AC XY: 6912 AN XY: 74472

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.0943

Gnomad4 ASJ AF: 0.0994

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.104 Hom.: 133

Bravo AF: 0.0915

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.82

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: rs2075173; hg19: chr14-81554617;