rs752047906

Variant names:

• chr11-77667000-C-G
• rs752047906
• NM_016578.4:c.4243G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-77667000-C-G
• chr11-77667000-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016578.4(RSF1):​c.4243G>C​(p.Ala1415Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A1415T) 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: 2.94
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22197989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSF1	NM_016578.4	c.4243G>C	p.Ala1415Pro	missense_variant	Exon 16 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.4234G>C	p.Ala1412Pro	missense_variant	Exon 16 of 16		XP_005274108.1
RSF1	XM_017017923.2	c.4120G>C	p.Ala1374Pro	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	c.4243G>C	p.Ala1415Pro	missense_variant	Exon 16 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.3487G>C	p.Ala1163Pro	missense_variant	Exon 11 of 11	1		ENSP00000434509.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459696 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725666

⚠️ 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: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39610

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110220

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000173), 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	Benign	0.21
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	0.81	L;.
PhyloP100		2.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.31	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.99	D;.
Vest4		0.26
MutPred		0.10		Gain of glycosylation at A1415 (P = 0.0452);.;
MVP		0.47
MPC		0.69
ClinPred		0.71	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.26
Mutation Taster		=81/19	polymorphism

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: rs752047906; hg19: chr11-77378045;