NM_000145.4:c.224+7375A>G

Variant names:

• chr2-49060844-T-C
• rs11686474
• NM_000145.4:c.224+7375A>G

Variant summary

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

The NM_000145.4(FSHR):​c.224+7375A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,002 control chromosomes in the GnomAD database, including 9,719 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 0.35 (9719 hom., cov: 31)
• Consequence: FSHR NM_000145.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 7 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

ENSG00000282890 (HGNC:58158):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHR	NM_000145.4	c.224+7375A>G		intron_variant	Intron 2 of 9	ENST00000406846.7	NP_000136.2
FSHR	NM_181446.3	c.224+7375A>G		intron_variant	Intron 2 of 8		NP_852111.2
FSHR	XM_011532733.3	c.224+7375A>G		intron_variant	Intron 2 of 10		XP_011531035.1
FSHR	XM_011532740.1	c.224+7375A>G		intron_variant	Intron 2 of 10		XP_011531042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHR	ENST00000406846.7	c.224+7375A>G		intron_variant	Intron 2 of 9	1	NM_000145.4	ENSP00000384708.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52586 AN: 151884 Hom.: 9712 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.346 AC: 52619 AN: 152002 Hom.: 9719 Cov.: 31 AF XY: 0.347 AC XY: 25796 AN XY: 74280

African (AFR) AF: 0.213 AC: 8834 AN: 41498

American (AMR) AF: 0.409 AC: 6249 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.489 AC: 2516 AN: 5142

South Asian (SAS) AF: 0.471 AC: 2271 AN: 4822

European-Finnish (FIN) AF: 0.314 AC: 3315 AN: 10558

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26964 AN: 67936

Other (OTH) AF: 0.375 AC: 791 AN: 2112

Alfa AF: 0.357 Hom.: 1696

Bravo AF: 0.346

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	10
DANN	Benign	0.32
PhyloP100		0.13
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: rs11686474; hg19: chr2-49287983;