2-49154560-T-C

Variant names:

• chr2-49154560-T-C
• rs2349718
• ENST00000634588.1:n.492+208155T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000634588.1(MIR548BAHG):​n.492+208155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 18)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: MIR548BAHG ENST00000634588.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 1 publications found

Genes affected

MIR548BAHG (HGNC:58158):

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634588.1. 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.-143A>G		upstream_gene	N/A	NP_000136.2
	FSHR	NM_181446.3		c.-143A>G		upstream_gene	N/A	NP_852111.2	P23945-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR548BAHG	ENST00000634588.1	TSL:5	n.492+208155T>C		intron	N/A
	FSHR	ENST00000406846.7	TSL:1 MANE Select	c.-143A>G		upstream_gene	N/A	ENSP00000384708.2	P23945-1
	FSHR	ENST00000304421.8	TSL:1	c.-143A>G		upstream_gene	N/A	ENSP00000306780.4	P23945-3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.000101 AC: 22 AN: 218214 Hom.: 0 Cov.: 0 AF XY: 0.000140 AC XY: 16 AN XY: 114492

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5590

American (AMR) AF: 0.000455 AC: 2 AN: 4392

Ashkenazi Jewish (ASJ) AF: 0.000137 AC: 1 AN: 7288

East Asian (EAS) AF: 0.00 AC: 0 AN: 6042

South Asian (SAS) AF: 0.000203 AC: 3 AN: 14756

European-Finnish (FIN) AF: 0.0000785 AC: 1 AN: 12738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 928

European-Non Finnish (NFE) AF: 0.0000836 AC: 13 AN: 155494

Other (OTH) AF: 0.000182 AC: 2 AN: 10986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000310862), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.31
PhyloP100		-0.56
PromoterAI		-0.016	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2349718; hg19: chr2-49381699;