11-30234276-A-G

Variant names:

• chr11-30234276-A-G
• rs506197
• NM_001382289.1:c.*476A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382289.1(FSHB):​c.*476A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 178,012 control chromosomes in the GnomAD database, including 21,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18643 hom., cov: 32)
  • Exomes 𝑓: 0.49 (3267 hom.)
• Consequence: FSHB NM_001382289.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0790

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-30234276-A-G is Benign according to our data. Variant chr11-30234276-A-G is described in ClinVar as [Benign]. Clinvar id is 304280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.*476A>G		3_prime_UTR_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.*476A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.*476A>G		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.*476A>G		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-77423T>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74776 AN: 151792 Hom.: 18631 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.487 AC: 12704 AN: 26104 Hom.: 3267 Cov.: 0 AF XY: 0.497 AC XY: 6620 AN XY: 13330

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome AF: 0.493 AC: 74825 AN: 151908 Hom.: 18643 Cov.: 32 AF XY: 0.500 AC XY: 37080 AN XY: 74228

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.469

Alfa AF: 0.435 Hom.: 6065

Bravo AF: 0.496

Asia WGS AF: 0.571 AC: 1983 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypogonadotropic hypogonadism 24 without anosmia Benign:1

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 provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.37

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: rs506197; hg19: chr11-30255823;