rs1394205

Variant names:

• chr2-49154446-C-T
• rs1394205
• NM_000145.4:c.-29G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-49154446-C-T
• chr2-49154446-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000145.4(FSHR):​c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,609,736 control chromosomes in the GnomAD database, including 70,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6505 hom., cov: 31)
  • Exomes 𝑓: 0.29 (64028 hom.)
• Consequence: FSHR NM_000145.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.730
• Publications: 102 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-49154446-C-T is Benign according to our data. Variant chr2-49154446-C-T is described in ClinVar as Benign. ClinVar VariationId is 137403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHR	NM_000145.4	MANE Select	c.-29G>A		5_prime_UTR	Exon 1 of 10	NP_000136.2
	FSHR	NM_181446.3		c.-29G>A		5_prime_UTR	Exon 1 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.-29G>A		5_prime_UTR	Exon 1 of 10	ENSP00000384708.2	P23945-1
	FSHR	ENST00000304421.8	TSL:1	c.-29G>A		5_prime_UTR	Exon 1 of 9	ENSP00000306780.4	P23945-3
	FSHR	ENST00000419927.1	TSL:1	n.-29G>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000405775.1	F8WBM4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43353 AN: 151800 Hom.: 6493 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.322 AC: 80116 AN: 249064 AF XY: 0.315

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.489

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.290 AC: 422620 AN: 1457818 Hom.: 64028 Cov.: 33 AF XY: 0.291 AC XY: 210771 AN XY: 725280

African (AFR) AF: 0.248 AC: 8279 AN: 33378

American (AMR) AF: 0.473 AC: 21107 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5645 AN: 26110

East Asian (EAS) AF: 0.480 AC: 19040 AN: 39664

South Asian (SAS) AF: 0.342 AC: 29445 AN: 86122

European-Finnish (FIN) AF: 0.278 AC: 14835 AN: 53340

Middle Eastern (MID) AF: 0.255 AC: 1059 AN: 4158

European-Non Finnish (NFE) AF: 0.276 AC: 305882 AN: 1110274

Other (OTH) AF: 0.288 AC: 17328 AN: 60138

GnomAD4 genome AF: 0.286 AC: 43405 AN: 151918 Hom.: 6505 Cov.: 31 AF XY: 0.288 AC XY: 21363 AN XY: 74240

African (AFR) AF: 0.252 AC: 10425 AN: 41440

American (AMR) AF: 0.370 AC: 5642 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2430 AN: 5140

South Asian (SAS) AF: 0.349 AC: 1678 AN: 4808

European-Finnish (FIN) AF: 0.271 AC: 2857 AN: 10554

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18682 AN: 67934

Other (OTH) AF: 0.286 AC: 603 AN: 2106

Alfa AF: 0.273 Hom.: 7336

Bravo AF: 0.294

Asia WGS AF: 0.423 AC: 1467 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Ovarian dysgenesis 1 (1)
-	-	1	Ovarian hyperstimulation syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		0.73
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	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: rs1394205; hg19: chr2-49381585; COSMIC: COSV58618032; COSMIC: COSV58618032;