chr11-30234276-A-G

Variant names:

• chr11-30234276-A-G
• rs506197
• NM_001382289.1:c.*476A>G

Variant summary

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

The NM_001382289.1(FSHB):​c.*476A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 178,012 control chromosomes in the GnomAD database, including 21,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18643 hom., cov: 32)
  • Exomes 𝑓: 0.49 (3267 hom.)
• Consequence: FSHB NM_001382289.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0790
• Publications: 8 publications found

Genes affected

FSHB (HGNC:3964): (follicle stimulating hormone subunit beta) The pituitary glycoprotein hormone family includes follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid-stimulating hormone. All of these glycoproteins consist of an identical alpha subunit and a hormone-specific beta subunit. This gene encodes the beta subunit of follicle-stimulating hormone. In conjunction with luteinizing hormone, follicle-stimulating hormone induces egg and sperm production. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ARL14EP-DT (HGNC:55517): (ARL14EP divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-30234276-A-G is Benign according to our data. Variant chr11-30234276-A-G is described in ClinVar as Benign. ClinVar VariationId is 304280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382289.1. 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
	FSHB	NM_001382289.1	MANE Select	c.*476A>G		3_prime_UTR	Exon 3 of 3	NP_001369218.1	A0A0F7RQE8
	FSHB	NM_000510.4		c.*476A>G		3_prime_UTR	Exon 3 of 3	NP_000501.1	P01225
	FSHB	NM_001018080.3		c.*476A>G		3_prime_UTR	Exon 3 of 3	NP_001018090.1	A0A0F7RQE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSHB	ENST00000533718.2	TSL:1 MANE Select	c.*476A>G		3_prime_UTR	Exon 3 of 3	ENSP00000433424.1	P01225
	FSHB	ENST00000254122.8	TSL:5	c.*476A>G		3_prime_UTR	Exon 3 of 3	ENSP00000254122.3	P01225
	FSHB	ENST00000417547.1	TSL:5	c.*476A>G		3_prime_UTR	Exon 3 of 3	ENSP00000416606.1	P01225

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74776 AN: 151792 Hom.: 18631 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.487 AC: 12704 AN: 26104 Hom.: 3267 Cov.: 0 AF XY: 0.497 AC XY: 6620 AN XY: 13330

African (AFR) AF: 0.535 AC: 381 AN: 712

American (AMR) AF: 0.527 AC: 1628 AN: 3090

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 255 AN: 534

East Asian (EAS) AF: 0.666 AC: 1381 AN: 2074

South Asian (SAS) AF: 0.574 AC: 1681 AN: 2930

European-Finnish (FIN) AF: 0.469 AC: 377 AN: 804

Middle Eastern (MID) AF: 0.475 AC: 38 AN: 80

European-Non Finnish (NFE) AF: 0.434 AC: 6341 AN: 14598

Other (OTH) AF: 0.485 AC: 622 AN: 1282

GnomAD4 genome AF: 0.493 AC: 74825 AN: 151908 Hom.: 18643 Cov.: 32 AF XY: 0.500 AC XY: 37080 AN XY: 74228

African (AFR) AF: 0.554 AC: 22948 AN: 41416

American (AMR) AF: 0.518 AC: 7917 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3466

East Asian (EAS) AF: 0.675 AC: 3467 AN: 5140

South Asian (SAS) AF: 0.568 AC: 2733 AN: 4808

European-Finnish (FIN) AF: 0.515 AC: 5432 AN: 10542

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.431 AC: 29295 AN: 67950

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.442 Hom.: 7481

Bravo AF: 0.496

Asia WGS AF: 0.571 AC: 1983 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypogonadotropic hypogonadism 24 without anosmia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		-0.079
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: rs506197; hg19: chr11-30255823;