Genetic Variant FSHB:c.-37-95A>T (chr11-30231771-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382289.1(FSHB):c.-37-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 949,642 control chromosomes in the GnomAD database, including 100,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17511 hom., cov: 32)

Exomes 𝑓: 0.45 ( 83207 hom. )

Consequence

FSHB
NM_001382289.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.36

Publications

7 publications found

Variant links:

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]

FSHB links:

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

ARL14EP-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-30231771-A-T is Benign according to our data. Variant chr11-30231771-A-T is described in ClinVar as Benign. ClinVar VariationId is 1271122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSHB	NM_001382289.1	MANE Select	c.-37-95A>T	intron	N/A	NP_001369218.1	A0A0F7RQE8
FSHB	NM_000510.4		c.-6-126A>T	intron	N/A	NP_000501.1	P01225
FSHB	NM_001018080.3		c.-6-126A>T	intron	N/A	NP_001018090.1	A0A0F7RQE8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSHB	ENST00000533718.2	TSL:1 MANE Select	c.-37-95A>T	intron	N/A	ENSP00000433424.1	P01225
FSHB	ENST00000254122.8	TSL:5	c.-6-126A>T	intron	N/A	ENSP00000254122.3	P01225
FSHB	ENST00000417547.1	TSL:5	c.-6-126A>T	intron	N/A	ENSP00000416606.1	P01225

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72622

AN:

151868

Hom.:

17505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.640

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

GnomAD4 exome

AF:

0.449

AC:

358468

AN:

797656

Hom.:

83207

AF XY:

0.455

AC XY:

189592

AN XY:

416384

show subpopulations

African (AFR)

AF:

0.542

AC:

10754

AN:

19850

American (AMR)

AF:

0.369

AC:

13192

AN:

35754

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

9572

AN:

20484

East Asian (EAS)

AF:

0.656

AC:

23177

AN:

35352

South Asian (SAS)

AF:

0.550

AC:

36707

AN:

66688

European-Finnish (FIN)

AF:

0.487

AC:

19596

AN:

40224

Middle Eastern (MID)

AF:

0.503

AC:

2194

AN:

4364

European-Non Finnish (NFE)

AF:

0.421

AC:

225916

AN:

536830

Other (OTH)

AF:

0.456

AC:

17360

AN:

38110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

9660

19319

28979

38638

48298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4614

9228

13842

18456

23070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.478

AC:

72662

AN:

151986

Hom.:

17511

Cov.:

AF XY:

0.484

AC XY:

35947

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.541

AC:

22393

AN:

41430

American (AMR)

AF:

0.439

AC:

6706

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

1613

AN:

3468

East Asian (EAS)

AF:

0.640

AC:

3299

AN:

5152

South Asian (SAS)

AF:

0.553

AC:

2673

AN:

4830

European-Finnish (FIN)

AF:

0.514

AC:

5426

AN:

10552

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.429

AC:

29162

AN:

67966

Other (OTH)

AF:

0.456

AC:

961

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1959

3917

5876

7834

9793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.454

Hom.:

1952

Bravo

AF:

0.474

Asia WGS

AF:

0.542

AC:

1882

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0010

(source)

DANN

Benign

0.54

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over