NM_018077.3:c.614-499C>T

Variant names:

• chr7-128336541-G-A
• rs359652
• NM_018077.3:c.614-499C>T

Variant summary

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

The NM_018077.3(RBM28):​c.614-499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,060 control chromosomes in the GnomAD database, including 24,922 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 0.55 (24922 hom., cov: 32)
• Consequence: RBM28 NM_018077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 4 publications found

Genes affected

RBM28 (HGNC:21863): (RNA binding motif protein 28) The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

RBM28 Gene-Disease associations (from GenCC):

• ANE syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM28	NM_018077.3	c.614-499C>T		intron_variant	Intron 6 of 18	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.191-499C>T		intron_variant	Intron 2 of 14		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.614-499C>T		intron_variant	Intron 6 of 18	1	NM_018077.3	ENSP00000223073.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83700 AN: 151942 Hom.: 24869 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.551 AC: 83808 AN: 152060 Hom.: 24922 Cov.: 32 AF XY: 0.543 AC XY: 40361 AN XY: 74334

African (AFR) AF: 0.777 AC: 32238 AN: 41490

American (AMR) AF: 0.453 AC: 6920 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3472

East Asian (EAS) AF: 0.189 AC: 980 AN: 5176

South Asian (SAS) AF: 0.474 AC: 2286 AN: 4822

European-Finnish (FIN) AF: 0.450 AC: 4745 AN: 10554

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33145 AN: 67964

Other (OTH) AF: 0.551 AC: 1161 AN: 2108

Alfa AF: 0.515 Hom.: 29146

Bravo AF: 0.561

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.70
PhyloP100		0.15
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: rs359652; hg19: chr7-127976595;