2-160357664-T-C

Variant names:

• chr2-160357664-T-C
• rs6718526
• NM_016836.4:c.251+9552A>G

Variant summary

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

The NM_016836.4(RBMS1):​c.251+9552A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,102 control chromosomes in the GnomAD database, including 53,108 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 0.83 (53108 hom., cov: 32)
• Consequence: RBMS1 NM_016836.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 18 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS1	NM_016836.4	MANE Select	c.251+9552A>G		intron	N/A	NP_058520.1	P29558-1
	RBMS1	NM_002897.5		c.251+9552A>G		intron	N/A	NP_002888.1	A0A0S2Z499

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS1	ENST00000348849.8	TSL:1 MANE Select	c.251+9552A>G		intron	N/A	ENSP00000294904.6	P29558-1
	RBMS1	ENST00000409075.5	TSL:1	c.152+9552A>G		intron	N/A	ENSP00000386347.1	E7ETU5
	RBMS1	ENST00000474820.5	TSL:1	n.377+9552A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126774 AN: 151984 Hom.: 53052 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.834 AC: 126883 AN: 152102 Hom.: 53108 Cov.: 32 AF XY: 0.836 AC XY: 62141 AN XY: 74348

African (AFR) AF: 0.871 AC: 36164 AN: 41508

American (AMR) AF: 0.855 AC: 13047 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2638 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4428 AN: 5166

South Asian (SAS) AF: 0.813 AC: 3924 AN: 4826

European-Finnish (FIN) AF: 0.850 AC: 9002 AN: 10592

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54980 AN: 67970

Other (OTH) AF: 0.818 AC: 1728 AN: 2112

Alfa AF: 0.818 Hom.: 87068

Bravo AF: 0.838

Asia WGS AF: 0.861 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.4
DANN	Benign	0.20
PhyloP100		0.40
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: rs6718526; hg19: chr2-161214175;