11-77667353-C-T

Variant summary

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

The NM_016578.4(RSF1):​c.3890G>A​(p.Arg1297His) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

RSF1
NM_016578.4 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15
Variant links:
Genes affected
RSF1 (HGNC:18118): (remodeling and spacing factor 1) This gene encodes a nuclear protein that interacts with hepatitis B virus X protein (HBX) and facilitates transcription of hepatitis B virus genes by the HBX transcription activator, suggesting a role for this interaction in the virus life cycle. This protein also interacts with SNF2H protein to form the RSF chromatin-remodeling complex, where the SNF2H subunit functions as the nucleosome-dependent ATPase, and this protein as the histone chaperone. [provided by RefSeq, Sep 2011]

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 GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSF1NM_016578.4 linkc.3890G>A p.Arg1297His missense_variant Exon 16 of 16 ENST00000308488.11 NP_057662.3 Q96T23-1Q05DG0
RSF1XM_005274051.3 linkc.3881G>A p.Arg1294His missense_variant Exon 16 of 16 XP_005274108.1
RSF1XM_017017923.2 linkc.3767G>A p.Arg1256His missense_variant Exon 16 of 16 XP_016873412.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSF1ENST00000308488.11 linkc.3890G>A p.Arg1297His missense_variant Exon 16 of 16 1 NM_016578.4 ENSP00000311513.6 Q96T23-1
RSF1ENST00000480887.5 linkc.3134G>A p.Arg1045His missense_variant Exon 11 of 11 1 ENSP00000434509.1 Q96T23-3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251218
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135772
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461694
Hom.:
0
Cov.:
32
AF XY:
0.0000234
AC XY:
17
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 27, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3890G>A (p.R1297H) alteration is located in exon 16 (coding exon 16) of the RSF1 gene. This alteration results from a G to A substitution at nucleotide position 3890, causing the arginine (R) at amino acid position 1297 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Uncertain
-0.070
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.080
T;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Uncertain
0.43
D
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.7
N;N
REVEL
Uncertain
0.45
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
D;.
Vest4
0.53
MVP
0.89
MPC
0.79
ClinPred
0.58
D
GERP RS
4.2
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.088
gMVP
0.26

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: rs781247505; hg19: chr11-77378398; COSMIC: COSV100407080; API