NM_000145.4:c.153-40835A>C

Variant names:

• chr2-49109125-T-G
• rs7606570
• NM_000145.4:c.153-40835A>C

Variant summary

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

The NM_000145.4(FSHR):​c.153-40835A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,844 control chromosomes in the GnomAD database, including 9,908 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9908 hom., cov: 32)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 0 publications found

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

MIR548BAHG (HGNC:58158):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.153-40835A>C		intron	N/A	NP_000136.2
	FSHR	NM_181446.3		c.153-40835A>C		intron	N/A	NP_852111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.153-40835A>C		intron	N/A	ENSP00000384708.2
	FSHR	ENST00000304421.8	TSL:1	c.153-40835A>C		intron	N/A	ENSP00000306780.4
	FSHR	ENST00000454032.5	TSL:1	c.153-40835A>C		intron	N/A	ENSP00000415504.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50841 AN: 151726 Hom.: 9876 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.335 AC: 50925 AN: 151844 Hom.: 9908 Cov.: 32 AF XY: 0.338 AC XY: 25061 AN XY: 74198

African (AFR) AF: 0.513 AC: 21250 AN: 41440

American (AMR) AF: 0.380 AC: 5802 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3458

East Asian (EAS) AF: 0.489 AC: 2488 AN: 5092

South Asian (SAS) AF: 0.315 AC: 1517 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2646 AN: 10538

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15633 AN: 67932

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.151 Hom.: 281

Bravo AF: 0.358

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.70
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7606570; hg19: chr2-49336264;