rs146571246

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002096.3(GTF2F1):​c.1511G>T​(p.Arg504Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R504H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GTF2F1
NM_002096.3 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.45
Variant links:
Genes affected
GTF2F1 (HGNC:4652): (general transcription factor IIF subunit 1) Enables several functions, including RNA polymerase II general transcription initiation factor activity; phosphatase activator activity; and promoter-specific chromatin binding activity. Involved in several processes, including positive regulation of transcription by RNA polymerase II; response to virus; and transcription initiation from RNA polymerase II promoter. Located in cell junction and nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF2F1NM_002096.3 linkc.1511G>T p.Arg504Leu missense_variant Exon 13 of 13 ENST00000394456.10 NP_002087.2 P35269
GTF2F1XM_047438710.1 linkc.1538G>T p.Arg513Leu missense_variant Exon 12 of 12 XP_047294666.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF2F1ENST00000394456.10 linkc.1511G>T p.Arg504Leu missense_variant Exon 13 of 13 1 NM_002096.3 ENSP00000377969.3 P35269
GTF2F1ENST00000593678.5 linkc.1259G>T p.Arg420Leu missense_variant Exon 10 of 10 2 ENSP00000469091.1 M0QXD6
GTF2F1ENST00000594213.5 linkn.868G>T non_coding_transcript_exon_variant Exon 6 of 6 3
GTF2F1ENST00000594965.1 linkn.*67G>T downstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251496
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Benign
-0.051
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.4
D;.
REVEL
Benign
0.25
Sift
Uncertain
0.013
D;.
Sift4G
Uncertain
0.012
D;D
Polyphen
0.99
D;.
Vest4
0.69
MutPred
0.54
Loss of MoRF binding (P = 0.0331);.;
MVP
0.75
MPC
1.0
ClinPred
0.92
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.54
gMVP
0.85

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146571246; hg19: chr19-6380335; API