dbSNP rs10835638: ARL14EP-DT:n.471-73952C>A (chr11-30230805-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.730

Publications

88 publications found

Variant links:

Genes affected

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

ARL14EP-DT links:

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

FSHB links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000527819.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

Gene	Transcript	HGVSc	Effect	Exon Rank
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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
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.:

show subpopulations

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.:

AF XY:

0.114

AC XY:

8506

AN XY:

74406

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10246

AN:

67992

Other (OTH)

AF:

0.118

AC:

250

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

808

1617

2425

3234

4042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

194

388

582

776

970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

1903

Bravo

AF:

0.113

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

ClinVar submissions

Significance:association

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypogonadotropic hypogonadism 24 without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

0.73

PromoterAI

0.0034

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over