11-77672182-C-G

Variant names:

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

Variant summary

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

The NM_016578.4(RSF1):​c.3611G>C​(p.Arg1204Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 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: 0.0000027 (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>C	p.Arg1204Pro	missense_variant	Exon 15 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3602G>C	p.Arg1201Pro	missense_variant	Exon 15 of 16		XP_005274108.1
RSF1	XM_017017923.2	c.3488G>C	p.Arg1163Pro	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>C	p.Arg1204Pro	missense_variant	Exon 15 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.2855G>C	p.Arg952Pro	missense_variant	Exon 10 of 11	1		ENSP00000434509.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459018 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725630

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00000360 AC: 4 AN: 1111240

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.0	M;.
PhyloP100		6.6
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.040	D;T
Polyphen		1.0	D;.
Vest4		0.63
MutPred		0.25		Gain of loop (P = 0.0013);.;
MVP		0.72
MPC		0.86
ClinPred		0.98	D
GERP RS		5.1
Varity_R		0.72
gMVP		0.36
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs577791059; hg19: chr11-77383227;