rs6169

Variant names:

• chr11-30233638-C-T
• rs6169
• NM_001382289.1:c.228C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-30233638-C-T
• chr11-30233638-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001382289.1(FSHB):​c.228C>T​(p.Tyr76Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,528 control chromosomes in the GnomAD database, including 182,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22994 hom., cov: 32)
  • Exomes 𝑓: 0.46 (159692 hom.)
• Consequence: FSHB NM_001382289.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.40
• Publications: 29 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-30233638-C-T is Benign according to our data. Variant chr11-30233638-C-T is described in ClinVar as Benign. ClinVar VariationId is 257061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.228C>T	p.Tyr76Tyr	synonymous	Exon 3 of 3	NP_001369218.1	A0A0F7RQE8
	FSHB	NM_000510.4		c.228C>T	p.Tyr76Tyr	synonymous	Exon 3 of 3	NP_000501.1	P01225
	FSHB	NM_001018080.3		c.228C>T	p.Tyr76Tyr	synonymous	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.228C>T	p.Tyr76Tyr	synonymous	Exon 3 of 3	ENSP00000433424.1	P01225
	FSHB	ENST00000254122.8	TSL:5	c.228C>T	p.Tyr76Tyr	synonymous	Exon 3 of 3	ENSP00000254122.3	P01225
	FSHB	ENST00000417547.1	TSL:5	c.228C>T	p.Tyr76Tyr	synonymous	Exon 3 of 3	ENSP00000416606.1	P01225

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81711 AN: 151874 Hom.: 22969 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.512 AC: 128318 AN: 250780 AF XY: 0.509

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.438

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.461 AC: 674149 AN: 1461534 Hom.: 159692 Cov.: 53 AF XY: 0.465 AC XY: 337836 AN XY: 727090

African (AFR) AF: 0.721 AC: 24139 AN: 33462

American (AMR) AF: 0.544 AC: 24320 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 12304 AN: 26130

East Asian (EAS) AF: 0.692 AC: 27436 AN: 39670

South Asian (SAS) AF: 0.574 AC: 49515 AN: 86254

European-Finnish (FIN) AF: 0.490 AC: 26180 AN: 53414

Middle Eastern (MID) AF: 0.521 AC: 3001 AN: 5764

European-Non Finnish (NFE) AF: 0.430 AC: 478349 AN: 1111762

Other (OTH) AF: 0.479 AC: 28905 AN: 60386

GnomAD4 genome AF: 0.538 AC: 81780 AN: 151994 Hom.: 22994 Cov.: 32 AF XY: 0.543 AC XY: 40347 AN XY: 74262

African (AFR) AF: 0.708 AC: 29342 AN: 41464

American (AMR) AF: 0.541 AC: 8266 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3472

East Asian (EAS) AF: 0.675 AC: 3481 AN: 5160

South Asian (SAS) AF: 0.578 AC: 2782 AN: 4812

European-Finnish (FIN) AF: 0.515 AC: 5434 AN: 10560

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29353 AN: 67942

Other (OTH) AF: 0.509 AC: 1073 AN: 2110

Alfa AF: 0.471 Hom.: 72688

Bravo AF: 0.546

Asia WGS AF: 0.582 AC: 2022 AN: 3476

EpiCase AF: 0.444

EpiControl AF: 0.436

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hypogonadotropic hypogonadism 24 without anosmia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.45
DANN	Benign	0.35
PhyloP100		-1.4
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: rs6169; hg19: chr11-30255185; COSMIC: COSV54221663;