11-77667403-C-T

Variant names:

• chr11-77667403-C-T
• rs11607608
• NM_016578.4:c.3840G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.878
• Publications: 5 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: 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	c.3840G>A	p.Glu1280Glu	synonymous_variant	Exon 16 of 16	ENST00000308488.11	NP_057662.3
RSF1	XM_005274051.3	c.3831G>A	p.Glu1277Glu	synonymous_variant	Exon 16 of 16		XP_005274108.1
RSF1	XM_017017923.2	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	c.3840G>A	p.Glu1280Glu	synonymous_variant	Exon 16 of 16	1	NM_016578.4	ENSP00000311513.6
RSF1	ENST00000480887.5	c.3084G>A	p.Glu1028Glu	synonymous_variant	Exon 11 of 11	1		ENSP00000434509.1

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 747 AN: 152186 Hom.: 4 Cov.: 32

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

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.: 44 Cov.: 32 AF XY: 0.00599 AC XY: 4357 AN XY: 727180

African (AFR) AF: 0.000836 AC: 28 AN: 33480

American (AMR) AF: 0.00230 AC: 103 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 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: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.00607 AC: 6754 AN: 1112004

Other (OTH) AF: 0.00525 AC: 317 AN: 60396

GnomAD4 genome AF: 0.00490 AC: 746 AN: 152304 Hom.: 4 Cov.: 32 AF XY: 0.00577 AC XY: 430 AN XY: 74466

African (AFR) AF: 0.00118 AC: 49 AN: 41568

American (AMR) AF: 0.00209 AC: 32 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.0228 AC: 242 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00584 AC: 397 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00382 Hom.: 1

Bravo AF: 0.00359

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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
DANN	Benign	0.46
PhyloP100		-0.88
Mutation Taster		=100/0	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: rs11607608; hg19: chr11-77378448;