rs4077463

Positions:

• chr2-160309723-A-G
• chr2-160309723-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000348849.8(RBMS1):​c.402+3433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,086 control chromosomes in the GnomAD database, including 42,935 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42935 hom., cov: 32)
• Consequence: RBMS1 ENST00000348849.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

RBMS1 (HGNC:9907): (RNA binding motif single stranded interacting protein 1) This gene encodes a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. Several transcript variants, resulting from alternative splicing and encoding different isoforms, have been described. A pseudogene for this locus is found on chromosome 12. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMS1	NM_016836.4	c.402+3433T>C		intron_variant		ENST00000348849.8	NP_058520.1
RBMS1	NM_002897.5	c.402+3433T>C		intron_variant			NP_002888.1
RBMS1	XM_047445368.1	c.402+3433T>C		intron_variant			XP_047301324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS1	ENST00000348849.8	c.402+3433T>C		intron_variant		1	NM_016836.4	ENSP00000294904	P1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113069 AN: 151968 Hom.: 42905 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.744 AC: 113149 AN: 152086 Hom.: 42935 Cov.: 32 AF XY: 0.748 AC XY: 55637 AN XY: 74358

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.761

Alfa AF: 0.785 Hom.: 53741

Bravo AF: 0.739

Asia WGS AF: 0.832 AC: 2886 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs4077463; hg19: chr2-161166234;