ENST00000662729.1:n.293-73952C>A

Variant names:

• chr11-30230805-G-T
• rs10835638
• ENST00000662729.1:n.293-73952C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000662729.1(ARL14EP-DT):​n.293-73952C>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 ENST00000662729.1 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.730

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.-281G>T		upstream_gene_variant		ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL14EP-DT	ENST00000662729.1	n.293-73952C>A		intron_variant	Intron 3 of 4
FSHB	ENST00000533718.2	c.-281G>T		upstream_gene_variant		1	NM_001382289.1	ENSP00000433424.1
FSHB	ENST00000254122.8	c.-280G>T		upstream_gene_variant		5		ENSP00000254122.3
FSHB	ENST00000417547.1	c.-250G>T		upstream_gene_variant		5		ENSP00000416606.1

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

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0655 Hom.: 74

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

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Gromoll Lab CeRA, University of Muenster

Significance: association

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	19
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10835638; hg19: chr11-30252352;