rs359652

Positions:

• chr7-128336541-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RBM28	NM_018077.3	c.614-499C>T		intron_variant		ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.191-499C>T		intron_variant			NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.614-499C>T		intron_variant		1	NM_018077.3	ENSP00000223073	P1

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

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.551

Alfa AF: 0.511 Hom.: 19848

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs359652; hg19: chr7-127976595;