11-30231771-A-T

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.-37-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 949,642 control chromosomes in the GnomAD database, including 100,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17511 hom., cov: 32)
  • Exomes 𝑓: 0.45 (83207 hom.)
• Consequence: FSHB NM_001382289.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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 11-30231771-A-T is Benign according to our data. Variant chr11-30231771-A-T is described in ClinVar as [Benign]. Clinvar id is 1271122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FSHB	NM_001382289.1	c.-37-95A>T		intron_variant		ENST00000533718.2
ARL14EP-DT	XR_007062639.1	n.351+85119T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FSHB	ENST00000533718.2	c.-37-95A>T		intron_variant		1	NM_001382289.1	P1
ARL14EP-DT	ENST00000662729.1	n.293-74918T>A		intron_variant, non_coding_transcript_variant
FSHB	ENST00000254122.8	c.-6-126A>T		intron_variant		5		P1
FSHB	ENST00000417547.1	c.-6-126A>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72622 AN: 151868 Hom.: 17505 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.449 AC: 358468 AN: 797656 Hom.: 83207 AF XY: 0.455 AC XY: 189592 AN XY: 416384

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.478 AC: 72662 AN: 151986 Hom.: 17511 Cov.: 32 AF XY: 0.484 AC XY: 35947 AN XY: 74296

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.456

Alfa AF: 0.454 Hom.: 1952

Bravo AF: 0.474

Asia WGS AF: 0.542 AC: 1882 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

Mar 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0010
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs611246; hg19: chr11-30253318; COSMIC: COSV54222264; COSMIC: COSV54222264;