2-48962622-A-T

Variant names:

• chr2-48962622-A-T
• rs140106399
• NM_000145.4:c.*111T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000145.4(FSHR):​c.*111T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 956,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FSHR NM_000145.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*111T>A		3_prime_UTR	Exon 10 of 10	NP_000136.2
	FSHR	NM_181446.3		c.*111T>A		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.*111T>A		3_prime_UTR	Exon 10 of 10	ENSP00000384708.2	P23945-1
	MIR548BAHG	ENST00000634588.1	TSL:5	n.492+16217A>T		intron	N/A
	FSHR	ENST00000304421.8	TSL:1	c.*111T>A		downstream_gene	N/A	ENSP00000306780.4	P23945-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 2 AN: 956270 Hom.: 0 Cov.: 13 AF XY: 0.00000203 AC XY: 1 AN XY: 492606

African (AFR) AF: 0.00 AC: 0 AN: 23426

American (AMR) AF: 0.00 AC: 0 AN: 39226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22220

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.00 AC: 0 AN: 70596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3514

European-Non Finnish (NFE) AF: 0.00000297 AC: 2 AN: 674328

Other (OTH) AF: 0.00 AC: 0 AN: 43600

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.36

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: rs140106399; hg19: chr2-49189761;