rs2304033

Variant names:

• chr5-146260424-A-G
• rs2304033
• NM_018989.2:c.1740-321A>G

Variant summary

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

The NM_018989.2(RBM27):​c.1740-321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,156 control chromosomes in the GnomAD database, including 4,248 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 0.21 (4248 hom., cov: 32)
• Consequence: RBM27 NM_018989.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 7 publications found

Genes affected

RBM27 (HGNC:29243): (RNA binding motif protein 27) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be located in cytoplasm and nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000275740 (HGNC:58349):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018989.2. 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
	RBM27	NM_018989.2	MANE Select	c.1740-321A>G		intron	N/A	NP_061862.1	Q9P2N5
	RBM27-POU4F3	NM_001414499.1		c.1575-321A>G		intron	N/A	NP_001401428.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM27	ENST00000265271.7	TSL:1 MANE Select	c.1740-321A>G		intron	N/A	ENSP00000265271.5	Q9P2N5
	ENSG00000275740	ENST00000506502.2	TSL:5	c.1575-321A>G		intron	N/A	ENSP00000475384.1	U3KPZ7
	RBM27	ENST00000861565.1		c.1743-321A>G		intron	N/A	ENSP00000531624.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31858 AN: 152036 Hom.: 4234 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.210 AC: 31879 AN: 152156 Hom.: 4248 Cov.: 32 AF XY: 0.211 AC XY: 15663 AN XY: 74372

African (AFR) AF: 0.0508 AC: 2113 AN: 41564

American (AMR) AF: 0.332 AC: 5073 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1156 AN: 5174

South Asian (SAS) AF: 0.164 AC: 789 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3134 AN: 10552

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18161 AN: 67982

Other (OTH) AF: 0.208 AC: 438 AN: 2110

Alfa AF: 0.246 Hom.: 2584

Bravo AF: 0.210

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.44
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2304033;

hg19: chr5-145639987;