Genetic Variant RSF1:p.Glu1292Lys (chr11-77667369-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016578.4(RSF1):c.3874G>A(p.Glu1292Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RSF1
NM_016578.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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]

RSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22479719).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4 link	c.3874G>A	p.Glu1292Lys	missense_variant	Exon 16 of 16	ENST00000308488.11	NP_057662.3	Q96T23-1Q05DG0
RSF1	XM_005274051.3 link	c.3865G>A	p.Glu1289Lys	missense_variant	Exon 16 of 16		XP_005274108.1
RSF1	XM_017017923.2 link	c.3751G>A	p.Glu1251Lys	missense_variant	Exon 16 of 16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11 link	c.3874G>A	p.Glu1292Lys	missense_variant	Exon 16 of 16	1	NM_016578.4	ENSP00000311513.6		Q96T23-1
RSF1	ENST00000480887.5 link	c.3118G>A	p.Glu1040Lys	missense_variant	Exon 11 of 11	1		ENSP00000434509.1		Q96T23-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251248

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135786

show subpopulations

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.0000297

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3874G>A (p.E1292K) 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 3874, causing the glutamic acid (E) at amino acid position 1292 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Benign

0.0015

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.081

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.86

N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.94

P;.

Vest4

0.26

MutPred

0.14

Gain of ubiquitination at E1292 (P = 0.009);.;

MVP

0.56

MPC

0.38

ClinPred

0.46

GERP RS

4.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.17

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over