rs611246

Variant names:

• chr11-30231771-A-T
• rs611246
• NM_001382289.1:c.-37-95A>T

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.-37-95A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 949,642 control chromosomes in the GnomAD database, including 100,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (17511 hom., cov: 32)
  • Exomes 𝑓: 0.45 (83207 hom.)
• Consequence: FSHB NM_001382289.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 7 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=-0.92).
• BP6: Variant 11-30231771-A-T is Benign according to our data. Variant chr11-30231771-A-T is described in ClinVar as Benign. ClinVar VariationId is 1271122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSHB	NM_001382289.1	c.-37-95A>T		intron_variant	Intron 1 of 2	ENST00000533718.2	NP_001369218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSHB	ENST00000533718.2	c.-37-95A>T		intron_variant	Intron 1 of 2	1	NM_001382289.1	ENSP00000433424.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72622 AN: 151868 Hom.: 17505 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.449 AC: 358468 AN: 797656 Hom.: 83207 AF XY: 0.455 AC XY: 189592 AN XY: 416384

African (AFR) AF: 0.542 AC: 10754 AN: 19850

American (AMR) AF: 0.369 AC: 13192 AN: 35754

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 9572 AN: 20484

East Asian (EAS) AF: 0.656 AC: 23177 AN: 35352

South Asian (SAS) AF: 0.550 AC: 36707 AN: 66688

European-Finnish (FIN) AF: 0.487 AC: 19596 AN: 40224

Middle Eastern (MID) AF: 0.503 AC: 2194 AN: 4364

European-Non Finnish (NFE) AF: 0.421 AC: 225916 AN: 536830

Other (OTH) AF: 0.456 AC: 17360 AN: 38110

GnomAD4 genome AF: 0.478 AC: 72662 AN: 151986 Hom.: 17511 Cov.: 32 AF XY: 0.484 AC XY: 35947 AN XY: 74296

African (AFR) AF: 0.541 AC: 22393 AN: 41430

American (AMR) AF: 0.439 AC: 6706 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1613 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3299 AN: 5152

South Asian (SAS) AF: 0.553 AC: 2673 AN: 4830

European-Finnish (FIN) AF: 0.514 AC: 5426 AN: 10552

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29162 AN: 67966

Other (OTH) AF: 0.456 AC: 961 AN: 2108

Alfa AF: 0.454 Hom.: 1952

Bravo AF: 0.474

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.54
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs611246; hg19: chr11-30253318; COSMIC: COSV54222264; COSMIC: COSV54222264;