rs10279576

Variant names:

• chr7-128325356-G-C
• rs10279576
• NM_018077.3:c.1203+462C>G

Variant summary

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

The NM_018077.3(RBM28):​c.1203+462C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,148 control chromosomes in the GnomAD database, including 7,355 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 0.29 (7355 hom., cov: 33)
• Consequence: RBM28 NM_018077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM28	NM_018077.3	c.1203+462C>G		intron_variant	Intron 11 of 18	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.780+462C>G		intron_variant	Intron 7 of 14		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.1203+462C>G		intron_variant	Intron 11 of 18	1	NM_018077.3	ENSP00000223073.1
RBM28	ENST00000415472.6	c.780+462C>G		intron_variant	Intron 7 of 14	2		ENSP00000390517.2
RBM28	ENST00000487602.5	n.545-662C>G		intron_variant	Intron 5 of 6	5		ENSP00000419840.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44666 AN: 152030 Hom.: 7347 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.294 AC: 44696 AN: 152148 Hom.: 7355 Cov.: 33 AF XY: 0.298 AC XY: 22153 AN XY: 74354

African (AFR) AF: 0.184 AC: 7648 AN: 41528

American (AMR) AF: 0.435 AC: 6650 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3472

East Asian (EAS) AF: 0.605 AC: 3126 AN: 5170

South Asian (SAS) AF: 0.339 AC: 1639 AN: 4828

European-Finnish (FIN) AF: 0.273 AC: 2884 AN: 10572

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20589 AN: 67986

Other (OTH) AF: 0.309 AC: 653 AN: 2110

Alfa AF: 0.291 Hom.: 832

Bravo AF: 0.304

Asia WGS AF: 0.460 AC: 1601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.57
PhyloP100		-0.38
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: rs10279576; hg19: chr7-127965409;