11-30233638-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382289.1(FSHB):c.228C>T(p.Tyr76Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,528 control chromosomes in the GnomAD database, including 182,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22994 hom., cov: 32)

Exomes 𝑓: 0.46 ( 159692 hom. )

Consequence

FSHB
NM_001382289.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.40

Publications

28 publications found

Variant links:

Genes affected

FSHB (HGNC:3964): (follicle stimulating hormone subunit beta) The pituitary glycoprotein hormone family includes follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid-stimulating hormone. All of these glycoproteins consist of an identical alpha subunit and a hormone-specific beta subunit. This gene encodes the beta subunit of follicle-stimulating hormone. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

FSHB links:

ARL14EP-DT (HGNC:55517): (ARL14EP divergent transcript)

ARL14EP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-30233638-C-T is Benign according to our data. Variant chr11-30233638-C-T is described in ClinVar as Benign. ClinVar VariationId is 257061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1 link	c.228C>T	p.Tyr76Tyr	synonymous_variant	Exon 3 of 3	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2 link	c.228C>T	p.Tyr76Tyr	synonymous_variant	Exon 3 of 3	1	NM_001382289.1	ENSP00000433424.1

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81711

AN:

151874

Hom.:

22969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.708

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.512

AC:

128318

AN:

250780

AF XY:

0.509

show subpopulations

Gnomad AFR exome

AF:

0.712

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.475

Gnomad EAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.501

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.461

AC:

674149

AN:

1461534

Hom.:

159692

Cov.:

AF XY:

0.465

AC XY:

337836

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.721

AC:

24139

AN:

33462

American (AMR)

AF:

0.544

AC:

24320

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

12304

AN:

26130

East Asian (EAS)

AF:

0.692

AC:

27436

AN:

39670

South Asian (SAS)

AF:

0.574

AC:

49515

AN:

86254

European-Finnish (FIN)

AF:

0.490

AC:

26180

AN:

53414

Middle Eastern (MID)

AF:

0.521

AC:

3001

AN:

5764

European-Non Finnish (NFE)

AF:

0.430

AC:

478349

AN:

1111762

Other (OTH)

AF:

0.479

AC:

28905

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

21529

43058

64586

86115

107644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14832

29664

44496

59328

74160

<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:

0.538

AC:

81780

AN:

151994

Hom.:

22994

Cov.:

AF XY:

0.543

AC XY:

40347

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.708

AC:

29342

AN:

41464

American (AMR)

AF:

0.541

AC:

8266

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1617

AN:

3472

East Asian (EAS)

AF:

0.675

AC:

3481

AN:

5160

South Asian (SAS)

AF:

0.578

AC:

2782

AN:

4812

European-Finnish (FIN)

AF:

0.515

AC:

5434

AN:

10560

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29353

AN:

67942

Other (OTH)

AF:

0.509

AC:

1073

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1874

3747

5621

7494

9368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.471

Hom.:

72688

Bravo

AF:

0.546

Asia WGS

AF:

0.582

AC:

2022

AN:

3476

EpiCase

AF:

0.444

EpiControl

AF:

0.436

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypogonadotropic hypogonadism 24 without anosmia

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.45

(source)

DANN

Benign

0.35

PhyloP100

-1.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over