chr3-87259906-A-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_000306.4(POU1F1):c.864T>A(p.Leu288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 1 hom. )
Consequence
POU1F1
NM_000306.4 synonymous
NM_000306.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.53
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
Variant 3-87259906-A-T is Benign according to our data. Variant chr3-87259906-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2966482.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.53 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000267 (39/1461416) while in subpopulation SAS AF= 0.000452 (39/86244). AF 95% confidence interval is 0.00034. There are 1 homozygotes in gnomad4_exome. There are 29 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POU1F1 | NM_000306.4 | c.864T>A | p.Leu288= | synonymous_variant | 6/6 | ENST00000350375.7 | |
POU1F1 | NM_001122757.3 | c.942T>A | p.Leu314= | synonymous_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POU1F1 | ENST00000350375.7 | c.864T>A | p.Leu288= | synonymous_variant | 6/6 | 1 | NM_000306.4 | P4 | |
POU1F1 | ENST00000344265.8 | c.942T>A | p.Leu314= | synonymous_variant | 6/6 | 5 | A1 | ||
POU1F1 | ENST00000561167.5 | c.639T>A | p.Leu213= | synonymous_variant | 5/5 | 5 | |||
POU1F1 | ENST00000560656.1 | c.*128T>A | 3_prime_UTR_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152214
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250682Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135610
GnomAD3 exomes
AF:
AC:
16
AN:
250682
Hom.:
AF XY:
AC XY:
11
AN XY:
135610
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461416Hom.: 1 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727038
GnomAD4 exome
AF:
AC:
39
AN:
1461416
Hom.:
Cov.:
31
AF XY:
AC XY:
29
AN XY:
727038
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
GnomAD4 genome
?
AF:
AC:
2
AN:
152214
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74358
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at