rs300977

chr3-87273910-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU1F1	NM_000306.4	c.143-492G>A		intron_variant		ENST00000350375.7
POU1F1	NM_001122757.3	c.143-414G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU1F1	ENST00000350375.7	c.143-492G>A		intron_variant		1	NM_000306.4	P4
POU1F1	ENST00000344265.8	c.143-414G>A		intron_variant		5		A1
POU1F1	ENST00000560656.1	c.143-492G>A		intron_variant		5
POU1F1	ENST00000561167.5	c.143-492G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.402

Alfa AF: 0.400 Hom.: 2925

Bravo AF: 0.386

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs300977; hg19: chr3-87323060;