rs80295823

Variant names:

• chr2-48962170-A-G
• rs80295823
• NM_000145.4:c.*563T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000145.4(FSHR):​c.*563T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 169,798 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FSHR NM_000145.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.342
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-48962170-A-G is Benign according to our data. Variant chr2-48962170-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 336474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00302 (460/152324) while in subpopulation AFR AF = 0.0107 (445/41576). AF 95% confidence interval is 0.00988. There are 2 homozygotes in GnomAd4. There are 209 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.*563T>C		3_prime_UTR	Exon 10 of 10	NP_000136.2
	FSHR	NM_181446.3		c.*563T>C		3_prime_UTR	Exon 9 of 9	NP_852111.2	P23945-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.*563T>C		3_prime_UTR	Exon 10 of 10	ENSP00000384708.2	P23945-1
	MIR548BAHG	ENST00000634588.1	TSL:5	n.492+15765A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 460 AN: 152206 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000114 AC: 2 AN: 17474 Hom.: 0 Cov.: 0 AF XY: 0.000105 AC XY: 1 AN XY: 9558

African (AFR) AF: 0.00 AC: 0 AN: 94

American (AMR) AF: 0.000773 AC: 2 AN: 2586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 168

East Asian (EAS) AF: 0.00 AC: 0 AN: 872

South Asian (SAS) AF: 0.00 AC: 0 AN: 2290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10336

Other (OTH) AF: 0.00 AC: 0 AN: 702

GnomAD4 genome AF: 0.00302 AC: 460 AN: 152324 Hom.: 2 Cov.: 32 AF XY: 0.00281 AC XY: 209 AN XY: 74484

African (AFR) AF: 0.0107 AC: 445 AN: 41576

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00420 Hom.: 0

Bravo AF: 0.00356

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ovarian dysgenesis 1 (1)
-	-	1	Ovarian hyperstimulation syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.4
DANN	Benign	0.80
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

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: rs80295823; hg19: chr2-49189309;