2-160287544-G-A

Variant names:

• chr2-160287544-G-A
• rs1020731
• NM_016836.4:c.641-460C>T

Variant summary

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

The NM_016836.4(RBMS1):​c.641-460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,112 control chromosomes in the GnomAD database, including 36,857 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 0.69 (36857 hom., cov: 32)
• Consequence: RBMS1 NM_016836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS1	NM_016836.4	c.641-460C>T		intron_variant	Intron 6 of 13	ENST00000348849.8	NP_058520.1
RBMS1	NM_002897.5	c.641-460C>T		intron_variant	Intron 6 of 13		NP_002888.1
RBMS1	XM_047445368.1	c.641-460C>T		intron_variant	Intron 6 of 13		XP_047301324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS1	ENST00000348849.8	c.641-460C>T		intron_variant	Intron 6 of 13	1	NM_016836.4	ENSP00000294904.6

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104966 AN: 151994 Hom.: 36818 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.691 AC: 105055 AN: 152112 Hom.: 36857 Cov.: 32 AF XY: 0.696 AC XY: 51767 AN XY: 74382

African (AFR) AF: 0.593 AC: 24572 AN: 41432

American (AMR) AF: 0.766 AC: 11722 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1987 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4124 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3258 AN: 4826

European-Finnish (FIN) AF: 0.793 AC: 8405 AN: 10596

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48651 AN: 68002

Other (OTH) AF: 0.685 AC: 1445 AN: 2110

Alfa AF: 0.721 Hom.: 7076

Bravo AF: 0.687

Asia WGS AF: 0.751 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		0.33
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: rs1020731; hg19: chr2-161144055;