11-30231642-T-G

Variant names:

• chr11-30231642-T-G
• rs550312
• NM_001382289.1:c.-37-224T>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.-37-224T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,024 control chromosomes in the GnomAD database, including 17,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (17529 hom., cov: 33)
• Consequence: FSHB NM_001382289.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0740

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=-0.87).
• BP6: Variant 11-30231642-T-G is Benign according to our data. Variant chr11-30231642-T-G is described in ClinVar as [Benign]. Clinvar id is 1220841.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 rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.-37-224T>G		intron_variant	Intron 1 of 2	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2	c.-37-224T>G		intron_variant	Intron 1 of 2	1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.-6-255T>G		intron_variant	Intron 1 of 2	5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.-6-255T>G		intron_variant	Intron 1 of 2	5		ENSP00000416606.1
ARL14EP-DT	ENST00000662729.1	n.293-74789A>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72653 AN: 151906 Hom.: 17523 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.639

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72693 AN: 152024 Hom.: 17529 Cov.: 33 AF XY: 0.484 AC XY: 35951 AN XY: 74294

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: 0.455

Alfa AF: 0.454 Hom.: 1951

Bravo AF: 0.474

Asia WGS AF: 0.541 AC: 1878 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

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	-0.87
CADD	Benign	10
DANN	Benign	0.76

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: rs550312; hg19: chr11-30253189;