rs11953506

Variant names:

• chr5-146225072-G-A
• rs11953506
• NM_018989.2:c.303+1545G>A

Variant summary

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

The NM_018989.2(RBM27):​c.303+1545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,022 control chromosomes in the GnomAD database, including 4,606 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 0.23 (4606 hom., cov: 32)
• Consequence: RBM27 NM_018989.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 5 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 = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM27	NM_018989.2	c.303+1545G>A		intron_variant	Intron 3 of 20	ENST00000265271.7	NP_061862.1
RBM27-POU4F3	NM_001414499.1	c.303+1545G>A		intron_variant	Intron 3 of 19		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7	c.303+1545G>A		intron_variant	Intron 3 of 20	1	NM_018989.2	ENSP00000265271.5
ENSG00000275740	ENST00000506502.2	c.303+1545G>A		intron_variant	Intron 3 of 19	5		ENSP00000475384.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35181 AN: 151904 Hom.: 4586 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.232 AC: 35234 AN: 152022 Hom.: 4606 Cov.: 32 AF XY: 0.233 AC XY: 17285 AN XY: 74316

African (AFR) AF: 0.128 AC: 5303 AN: 41484

American (AMR) AF: 0.339 AC: 5175 AN: 15270

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

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5168

South Asian (SAS) AF: 0.163 AC: 789 AN: 4830

European-Finnish (FIN) AF: 0.299 AC: 3152 AN: 10546

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18180 AN: 67948

Other (OTH) AF: 0.221 AC: 466 AN: 2104

Alfa AF: 0.248 Hom.: 3194

Bravo AF: 0.235

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.16
PhyloP100		-0.78
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: rs11953506; hg19: chr5-145604635;