dbSNP rs2239610: TSHR:c.170+63G>C (chr14-80955913-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000369.5(TSHR):c.170+63G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,606,776 control chromosomes in the GnomAD database, including 55,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3802 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51553 hom. )

Consequence

TSHR
NM_000369.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0100

Publications

15 publications found

Variant links:

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]

TSHR links:

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]

CEP128 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-80955913-G-C is Benign according to our data. Variant chr14-80955913-G-C is described in ClinVar as Benign. ClinVar VariationId is 1234822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSHR	NM_000369.5	MANE Select	c.170+63G>C	intron	N/A	NP_000360.2	P16473-1
TSHR	NM_001142626.3		c.170+63G>C	intron	N/A	NP_001136098.1	P16473-3
TSHR	NM_001018036.3		c.170+63G>C	intron	N/A	NP_001018046.1	P16473-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSHR	ENST00000298171.7	TSL:1 MANE Select	c.170+63G>C	intron	N/A	ENSP00000298171.2	P16473-1
TSHR	ENST00000554435.1	TSL:1	c.170+63G>C	intron	N/A	ENSP00000450549.1	P16473-3
TSHR	ENST00000342443.10	TSL:1	c.170+63G>C	intron	N/A	ENSP00000340113.6	P16473-2

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32573

AN:

152128

Hom.:

3797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.262

AC:

381021

AN:

1454530

Hom.:

51553

Cov.:

AF XY:

0.259

AC XY:

187789

AN XY:

724008

show subpopulations

African (AFR)

AF:

0.109

AC:

3629

AN:

33346

American (AMR)

AF:

0.381

AC:

17040

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

6468

AN:

26104

East Asian (EAS)

AF:

0.227

AC:

9008

AN:

39672

South Asian (SAS)

AF:

0.213

AC:

18339

AN:

86034

European-Finnish (FIN)

AF:

0.179

AC:

9207

AN:

51542

Middle Eastern (MID)

AF:

0.187

AC:

1073

AN:

5746

European-Non Finnish (NFE)

AF:

0.272

AC:

301377

AN:

1107216

Other (OTH)

AF:

0.247

AC:

14880

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

15597

31194

46792

62389

77986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10188

20376

30564

40752

50940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.214

AC:

32591

AN:

152246

Hom.:

3802

Cov.:

AF XY:

0.210

AC XY:

15600

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.121

AC:

5043

AN:

41534

American (AMR)

AF:

0.283

AC:

4324

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3472

East Asian (EAS)

AF:

0.210

AC:

1087

AN:

5174

South Asian (SAS)

AF:

0.209

AC:

1007

AN:

4818

European-Finnish (FIN)

AF:

0.169

AC:

1791

AN:

10618

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17706

AN:

68014

Other (OTH)

AF:

0.223

AC:

470

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1338

2676

4015

5353

6691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.130

Hom.:

236

Bravo

AF:

0.222

Asia WGS

AF:

0.247

AC:

861

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.55

PhyloP100

-0.010

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over