rs609896

chr11-30232094-T-Cchr11-30232094-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001382289.1(FSHB):c.159+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,608,472 control chromosomes in the GnomAD database, including 173,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18667 hom., cov: 33)
  • Exomes 𝑓: 0.46 (154558 hom.)
• Consequence: FSHB NM_001382289.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.97

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-30232094-T-C is Benign according to our data. Variant chr11-30232094-T-C is described in ClinVar as [Benign]. Clinvar id is 1243392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHB	NM_001382289.1	c.159+33T>C		intron_variant		ENST00000533718.2
ARL14EP-DT	XR_007062639.1	n.351+84796A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHB	ENST00000533718.2	c.159+33T>C		intron_variant		1	NM_001382289.1	P1
ARL14EP-DT	ENST00000662729.1	n.293-75241A>G		intron_variant, non_coding_transcript_variant
FSHB	ENST00000254122.8	c.159+33T>C		intron_variant		5		P1
FSHB	ENST00000417547.1	c.159+33T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74863 AN: 152030 Hom.: 18654 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.471

GnomAD3 exomes AF: 0.499 AC: 124610 AN: 249818 Hom.: 31782 AF XY: 0.499 AC XY: 67381 AN XY: 135042

Gnomad AFR exome AF: 0.555

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.669

Gnomad SAS exome AF: 0.565

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.437

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.456 AC: 663760 AN: 1456324 Hom.: 154558 Cov.: 32 AF XY: 0.460 AC XY: 333126 AN XY: 724788

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.692

Gnomad4 SAS exome AF: 0.568

Gnomad4 FIN exome AF: 0.490

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.492 AC: 74917 AN: 152148 Hom.: 18667 Cov.: 33 AF XY: 0.499 AC XY: 37143 AN XY: 74380

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.469

Alfa AF: 0.463 Hom.: 3568

Bravo AF: 0.496

Asia WGS AF: 0.572 AC: 1986 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.35
Dann	Benign	0.39

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: rs609896; hg19: chr11-30253641; COSMIC: COSV54222415;