rs2268451

Variant names:

• chr14-80957774-T-G
• rs2268451
• NM_000369.5:c.170+1924T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000369.5(TSHR):​c.170+1924T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,098 control chromosomes in the GnomAD database, including 20,489 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 0.50 (20487 hom., cov: 32)
  • Exomes 𝑓: 0.38 (2 hom.)
• Consequence: TSHR NM_000369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 8 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]

CEP128 (HGNC:20359): (centrosomal protein 128) Involved in protein localization. Located in centriole and spindle pole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000369.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHR	NM_000369.5	MANE Select	c.170+1924T>G		intron	N/A	NP_000360.2	P16473-1
	TSHR	NM_001142626.3		c.170+1924T>G		intron	N/A	NP_001136098.1	P16473-3
	TSHR	NM_001018036.3		c.170+1924T>G		intron	N/A	NP_001018046.1	P16473-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSHR	ENST00000298171.7	TSL:1 MANE Select	c.170+1924T>G		intron	N/A	ENSP00000298171.2	P16473-1
	TSHR	ENST00000554435.1	TSL:1	c.170+1924T>G		intron	N/A	ENSP00000450549.1	P16473-3
	TSHR	ENST00000342443.10	TSL:1	c.170+1924T>G		intron	N/A	ENSP00000340113.6	P16473-2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75788 AN: 151956 Hom.: 20457 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.495

GnomAD4 exome AF: 0.375 AC: 9 AN: 24 Hom.: 2 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.167 AC: 2 AN: 12

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.499 AC: 75864 AN: 152074 Hom.: 20487 Cov.: 32 AF XY: 0.490 AC XY: 36412 AN XY: 74344

African (AFR) AF: 0.707 AC: 29286 AN: 41450

American (AMR) AF: 0.447 AC: 6839 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5182

South Asian (SAS) AF: 0.501 AC: 2411 AN: 4814

European-Finnish (FIN) AF: 0.309 AC: 3265 AN: 10580

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.431 AC: 29315 AN: 67980

Other (OTH) AF: 0.491 AC: 1039 AN: 2114

Alfa AF: 0.474 Hom.: 2773

Bravo AF: 0.521

Asia WGS AF: 0.407 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.60
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2268451;

hg19: chr14-81424118;