rs300977

Variant names:

• chr3-87273910-C-T
• rs300977
• NM_000306.4:c.143-492G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000306.4(POU1F1):​c.143-492G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,964 control chromosomes in the GnomAD database, including 12,131 homozygotes. 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: 𝑓 0.39 (12131 hom., cov: 32)
• Consequence: POU1F1 NM_000306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 4 publications found

Genes affected

POU1F1 (HGNC:9210): (POU class 1 homeobox 1) This gene encodes a member of the POU family of transcription factors that regulate mammalian development. The protein regulates expression of several genes involved in pituitary development and hormone expression. Mutations in this genes result in combined pituitary hormone deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

POU1F1 Gene-Disease associations (from GenCC):

• pituitary hormone deficiency, combined, 1

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypothyroidism due to deficient transcription factors involved in pituitary development or function

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated growth hormone deficiency type II

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000306.4. 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
	POU1F1	NM_000306.4	MANE Select	c.143-492G>A		intron	N/A	NP_000297.1	P28069-1
	POU1F1	NM_001122757.3		c.143-414G>A		intron	N/A	NP_001116229.1	P28069-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU1F1	ENST00000350375.7	TSL:1 MANE Select	c.143-492G>A		intron	N/A	ENSP00000263781.2	P28069-1
	POU1F1	ENST00000344265.8	TSL:5	c.143-414G>A		intron	N/A	ENSP00000342931.3	P28069-2
	POU1F1	ENST00000561167.5	TSL:5	c.143-492G>A		intron	N/A	ENSP00000454072.1	H0YNM5

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59525 AN: 151846 Hom.: 12124 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59570 AN: 151964 Hom.: 12131 Cov.: 32 AF XY: 0.399 AC XY: 29661 AN XY: 74266

African (AFR) AF: 0.291 AC: 12047 AN: 41434

American (AMR) AF: 0.458 AC: 6990 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2606 AN: 5172

South Asian (SAS) AF: 0.569 AC: 2739 AN: 4814

European-Finnish (FIN) AF: 0.432 AC: 4556 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27957 AN: 67944

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.402 Hom.: 5410

Bravo AF: 0.386

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.42
PhyloP100		0.56
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: rs300977; hg19: chr3-87323060;