11-30230805-G-T

Variant names:

• chr11-30230805-G-T
• rs10835638
• ENST00000527819.2:n.471-73952C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000527819.2(ARL14EP-DT):​n.471-73952C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,196 control chromosomes in the GnomAD database, including 1,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.12 (1134 hom., cov: 33)
• Consequence: ARL14EP-DT ENST00000527819.2 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.730
• Publications: 86 publications found

Genes affected

ARL14EP-DT (HGNC:55517): (ARL14EP divergent transcript)

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]

FSHB Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 24 without anosmia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527819.2. 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
	ARL14EP-DT	NR_187431.1		n.250+86085C>A		intron	N/A
	ARL14EP-DT	NR_187432.1		n.429+86085C>A		intron	N/A
	ARL14EP-DT	NR_187433.1		n.250+86085C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL14EP-DT	ENST00000527819.2	TSL:3	n.471-73952C>A		intron	N/A
	ARL14EP-DT	ENST00000662729.1		n.293-73952C>A		intron	N/A
	ARL14EP-DT	ENST00000726808.1		n.517-73952C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17665 AN: 152076 Hom.: 1131 Cov.: 33

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.116 AC: 17671 AN: 152196 Hom.: 1134 Cov.: 33 AF XY: 0.114 AC XY: 8506 AN XY: 74406

African (AFR) AF: 0.0636 AC: 2642 AN: 41538

American (AMR) AF: 0.126 AC: 1920 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.0338 AC: 175 AN: 5174

South Asian (SAS) AF: 0.101 AC: 487 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1402 AN: 10592

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10246 AN: 67992

Other (OTH) AF: 0.118 AC: 250 AN: 2110

Alfa AF: 0.133 Hom.: 1903

Bravo AF: 0.113

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypogonadotropic hypogonadism 24 without anosmia Other:1

Gromoll Lab CeRA, University of Muenster

Significance: association

Review Status: no assertion criteria provided

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.57
PhyloP100		0.73
PromoterAI		0.0034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10835638; hg19: chr11-30252352;