chr11-30232094-T-C

Variant names:

• chr11-30232094-T-C
• rs609896
• NM_001382289.1:c.159+33T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1243392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382289.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHB	NM_001382289.1	MANE Select	c.159+33T>C		intron	N/A	NP_001369218.1
	FSHB	NM_000510.4		c.159+33T>C		intron	N/A	NP_000501.1
	FSHB	NM_001018080.3		c.159+33T>C		intron	N/A	NP_001018090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHB	ENST00000533718.2	TSL:1 MANE Select	c.159+33T>C		intron	N/A	ENSP00000433424.1
	FSHB	ENST00000254122.8	TSL:5	c.159+33T>C		intron	N/A	ENSP00000254122.3
	FSHB	ENST00000417547.1	TSL:5	c.159+33T>C		intron	N/A	ENSP00000416606.1

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

GnomAD2 exomes AF: 0.499 AC: 124610 AN: 249818 AF XY: 0.499

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 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

African (AFR) AF: 0.563 AC: 18795 AN: 33366

American (AMR) AF: 0.534 AC: 23838 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 12279 AN: 26082

East Asian (EAS) AF: 0.692 AC: 27405 AN: 39628

South Asian (SAS) AF: 0.568 AC: 48923 AN: 86140

European-Finnish (FIN) AF: 0.490 AC: 25777 AN: 52632

Middle Eastern (MID) AF: 0.509 AC: 2896 AN: 5694

European-Non Finnish (NFE) AF: 0.429 AC: 475806 AN: 1107962

Other (OTH) AF: 0.466 AC: 28041 AN: 60170

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

African (AFR) AF: 0.553 AC: 22969 AN: 41506

American (AMR) AF: 0.519 AC: 7932 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1611 AN: 3466

East Asian (EAS) AF: 0.673 AC: 3482 AN: 5172

South Asian (SAS) AF: 0.569 AC: 2746 AN: 4826

European-Finnish (FIN) AF: 0.514 AC: 5436 AN: 10570

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29321 AN: 67998

Other (OTH) AF: 0.469 AC: 991 AN: 2114

Alfa AF: 0.466 Hom.: 3703

Bravo AF: 0.496

Asia WGS AF: 0.572 AC: 1986 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.39
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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