Genetic Variant RSF1:p.Glu1280Glu (chr11-77667403-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016578.4(RSF1):c.3840G>A(p.Glu1280Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 1,614,036 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 44 hom. )

Consequence

RSF1
NM_016578.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.878

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-77667403-C-T is Benign according to our data. Variant chr11-77667403-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642192.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.878 with no splicing effect.

BS2

High AC in GnomAd4 at 746 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4 link	c.3840G>A	p.Glu1280Glu	synonymous_variant	Exon 16 of 16	ENST00000308488.11	NP_057662.3	Q96T23-1Q05DG0
RSF1	XM_005274051.3 link	c.3831G>A	p.Glu1277Glu	synonymous_variant	Exon 16 of 16		XP_005274108.1
RSF1	XM_017017923.2 link	c.3717G>A	p.Glu1239Glu	synonymous_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.3840G>A	p.Glu1280Glu	synonymous_variant	Exon 16 of 16	1	NM_016578.4	ENSP00000311513.6		Q96T23-1
RSF1	ENST00000480887.5 link	c.3084G>A	p.Glu1028Glu	synonymous_variant	Exon 11 of 11	1		ENSP00000434509.1		Q96T23-3

Frequencies

GnomAD3 genomes

AF:

0.00491

AC:

747

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00585

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00507

AC:

1274

AN:

251164

AF XY:

0.00515

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0193

Gnomad NFE exome

AF:

0.00516

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00601

AC:

8791

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

4357

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00230

AC:

103

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00548

AC:

473

AN:

86258

European-Finnish (FIN)

AF:

0.0207

AC:

1101

AN:

53268

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00607

AC:

6754

AN:

1112004

Other (OTH)

AF:

0.00525

AC:

317

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

530

1060

1590

2120

2650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00490

AC:

746

AN:

152304

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

430

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41568

American (AMR)

AF:

0.00209

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00394

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0228

AC:

242

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00584

AC:

397

AN:

68026

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00359

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RSF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.2

(source)

DANN

Benign

0.46

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr11-77667403-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over