11-30233638-C-T

Position:

chr11-30233638-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382289.1(FSHB):c.228C>T(p.Tyr76=) 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
FSHB	NM_001382289.1 linkuse as main transcript	c.228C>T	p.Tyr76=	synonymous_variant	3/3	ENST00000533718.2
ARL14EP-DT	XR_007062639.1 linkuse as main transcript	n.351+83252G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FSHB	ENST00000533718.2 linkuse as main transcript	c.228C>T	p.Tyr76=	synonymous_variant	3/3	1	NM_001382289.1	P1
ARL14EP-DT	ENST00000662729.1 linkuse as main transcript	n.293-76785G>A		intron_variant, non_coding_transcript_variant
FSHB	ENST00000254122.8 linkuse as main transcript	c.228C>T	p.Tyr76=	synonymous_variant	3/3	5		P1
FSHB	ENST00000417547.1 linkuse as main transcript	c.228C>T	p.Tyr76=	synonymous_variant	3/3	5		P1

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

GnomAD3 exomes

AF:

0.512

AC:

128318

AN:

250780

Hom.:

33910

AF XY:

0.509

AC XY:

68947

AN XY:

135502

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 SAS exome

AF:

0.572

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

Gnomad4 AFR exome

AF:

0.721

Gnomad4 AMR exome

AF:

0.544

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.692

Gnomad4 SAS exome

AF:

0.574

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.430

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.538

AC:

81780

AN:

151994

Hom.:

22994

Cov.:

AF XY:

0.543

AC XY:

40347

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.708

Gnomad4 AMR

AF:

0.541

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.675

Gnomad4 SAS

AF:

0.578

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.432

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.459

Hom.:

33322

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Hypogonadotropic hypogonadism 24 without anosmia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.45

DANN

Benign

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over