2-160309723-A-G

Variant names:

• chr2-160309723-A-G
• rs4077463
• NM_016836.4:c.402+3433T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016836.4(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 NM_016836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBMS1	NM_016836.4	c.402+3433T>C		intron_variant	Intron 4 of 13	ENST00000348849.8	NP_058520.1
RBMS1	NM_002897.5	c.402+3433T>C		intron_variant	Intron 4 of 13		NP_002888.1
RBMS1	XM_047445368.1	c.402+3433T>C		intron_variant	Intron 4 of 13		XP_047301324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS1	ENST00000348849.8	c.402+3433T>C		intron_variant	Intron 4 of 13	1	NM_016836.4	ENSP00000294904.6

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

African (AFR) AF: 0.602 AC: 24960 AN: 41434

American (AMR) AF: 0.819 AC: 12508 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2427 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4315 AN: 5172

South Asian (SAS) AF: 0.801 AC: 3853 AN: 4810

European-Finnish (FIN) AF: 0.833 AC: 8837 AN: 10614

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53681 AN: 67988

Other (OTH) AF: 0.761 AC: 1607 AN: 2112

Alfa AF: 0.780 Hom.: 66013

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
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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: rs4077463; hg19: chr2-161166234;