11-30233638-C-T

Variant names:

• chr11-30233638-C-T
• rs6169
• NM_001382289.1:c.228C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.40

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]

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

ACMG classification

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 rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	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	c.228C>T	p.Tyr76Tyr	synonymous_variant	Exon 3 of 3	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.228C>T	p.Tyr76Tyr	synonymous_variant	Exon 3 of 3	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.228C>T	p.Tyr76Tyr	synonymous_variant	Exon 3 of 3	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-76785G>A		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81711 AN: 151874 Hom.: 22969 Cov.: 32

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

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.: 53 AF XY: 0.465 AC XY: 337836 AN XY: 727090

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.: 32 AF XY: 0.543 AC XY: 40347 AN XY: 74262

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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
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

Other links and lift over

dbSNP: rs6169; hg19: chr11-30255185; COSMIC: COSV54221663;