rs577791059

Variant names:

• chr11-77672182-C-A
• rs577791059
• NM_016578.4:c.3611G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-77672182-C-A
• chr11-77672182-C-G
• chr11-77672182-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016578.4(RSF1):​c.3611G>T​(p.Arg1204Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,018 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. R1204Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RSF1 NM_016578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4	c.3611G>T	p.Arg1204Leu	missense_variant	Exon 15 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3602G>T	p.Arg1201Leu	missense_variant	Exon 15 of 16		XP_005274108.1
RSF1	XM_017017923.2	c.3488G>T	p.Arg1163Leu	missense_variant	Exon 15 of 16		XP_016873412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSF1	ENST00000308488.11	c.3611G>T	p.Arg1204Leu	missense_variant	Exon 15 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.2855G>T	p.Arg952Leu	missense_variant	Exon 10 of 11	1		ENSP00000434509.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459018 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725630

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111240

Other (OTH) AF: 0.00 AC: 0 AN: 60310

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		6.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.048	D;T
Polyphen		1.0	D;.
Vest4		0.60
MutPred		0.25		Loss of MoRF binding (P = 0.0773);.;
MVP		0.79
MPC		0.79
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.30
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs577791059; hg19: chr11-77383227;