Genetic Variant NM_000145.4:c.*574T>C (chr2-48962159-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000145.4(FSHR):c.*574T>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 168,560 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

FSHR
NM_000145.4 splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.872

Publications

0 publications found

Variant links:

Genes affected

FSHR (HGNC:3969): (follicle stimulating hormone receptor) The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

FSHR Gene-Disease associations (from GenCC):

ovarian hyperstimulation syndrome
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ovarian dysgenesis 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FSHR links:

MIR548BAHG (HGNC:58158):

MIR548BAHG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSHR	NM_000145.4	MANE Select	c.*574T>C	splice_region	Exon 10 of 10	NP_000136.2
FSHR	NM_000145.4	MANE Select	c.*574T>C	3_prime_UTR	Exon 10 of 10	NP_000136.2
FSHR	NM_181446.3		c.*574T>C	splice_region	Exon 9 of 9	NP_852111.2	P23945-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSHR	ENST00000406846.7	TSL:1 MANE Select	c.*574T>C	splice_region	Exon 10 of 10	ENSP00000384708.2	P23945-1
FSHR	ENST00000406846.7	TSL:1 MANE Select	c.*574T>C	3_prime_UTR	Exon 10 of 10	ENSP00000384708.2	P23945-1
MIR548BAHG	ENST00000634588.1	TSL:5	n.492+15754A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000123

AC:

AN:

16298

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

AN XY:

9004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.000796

AC:

AN:

2512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

148

East Asian (EAS)

AF:

0.00

AC:

AN:

786

South Asian (SAS)

AF:

0.00

AC:

AN:

2034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

9728

Other (OTH)

AF:

0.00

AC:

AN:

634

Age Distribution

Exome Hom

Variant carriers

<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:

0.00205

AC:

312

AN:

152262

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00679

AC:

282

AN:

41556

American (AMR)

AF:

0.00105

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68010

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00244

Hom.:

Bravo

AF:

0.00251

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ovarian dysgenesis 1 (1)

Ovarian hyperstimulation syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.7

(source)

DANN

Benign

0.67

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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