chr5-146204060-A-G

Variant names:

• chr5-146204060-A-G
• rs2279895
• NM_018989.2:c.59+236A>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.59+236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,938 control chromosomes in the GnomAD database, including 5,183 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 0.25 (5183 hom., cov: 32)
• Consequence: RBM27 NM_018989.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 16 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM27	NM_018989.2	c.59+236A>G		intron_variant	Intron 1 of 20	ENST00000265271.7	NP_061862.1
RBM27-POU4F3	NM_001414499.1	c.59+236A>G		intron_variant	Intron 1 of 19		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM27	ENST00000265271.7	c.59+236A>G		intron_variant	Intron 1 of 20	1	NM_018989.2	ENSP00000265271.5
ENSG00000275740	ENST00000506502.2	c.59+236A>G		intron_variant	Intron 1 of 19	5		ENSP00000475384.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37803 AN: 151820 Hom.: 5163 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.249 AC: 37859 AN: 151938 Hom.: 5183 Cov.: 32 AF XY: 0.249 AC XY: 18519 AN XY: 74274

African (AFR) AF: 0.159 AC: 6593 AN: 41438

American (AMR) AF: 0.343 AC: 5233 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1092 AN: 5162

South Asian (SAS) AF: 0.172 AC: 829 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3306 AN: 10548

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19293 AN: 67908

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.271 Hom.: 9263

Bravo AF: 0.252

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.35
PromoterAI		-0.037	Neutral
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: rs2279895; hg19: chr5-145583623;