rs76296626

Positions:

• chr3-87260109-C-A
• chr3-87260109-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000350375.7(POU1F1):​c.666-5G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: POU1F1 ENST00000350375.7 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002458
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.899

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU1F1	NM_000306.4	c.666-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000350375.7	NP_000297.1
POU1F1	NM_001122757.3	c.744-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001116229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU1F1	ENST00000350375.7	c.666-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000306.4	ENSP00000263781	P4
POU1F1	ENST00000344265.8	c.744-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000342931	A1
POU1F1	ENST00000560656.1	c.440-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000452610
POU1F1	ENST00000561167.5	c.441-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000454072

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 243964 Hom.: 0 AF XY: 0.00000756 AC XY: 1 AN XY: 132210

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000915

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458642 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.012
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: rs76296626; hg19: chr3-87309259;