rs12850

Positions:

• chr7-128310672-G-A
• chr7-128310672-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018077.3(RBM28):​c.*125C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,304,646 control chromosomes in the GnomAD database, including 85,946 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 0.31 (8420 hom., cov: 31)
  • Exomes 𝑓: 0.36 (77526 hom.)
• Consequence: RBM28 NM_018077.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3	c.*125C>T		3_prime_UTR_variant	19/19	ENST00000223073.6
RBM28	NM_001166135.2	c.*125C>T		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6	c.*125C>T		3_prime_UTR_variant	19/19	1	NM_018077.3	P1
RBM28	ENST00000415472.6	c.*125C>T		3_prime_UTR_variant	15/15	2
RBM28	ENST00000481788.1	n.777C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46912 AN: 151904 Hom.: 8411 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.359 AC: 413448 AN: 1152624 Hom.: 77526 Cov.: 16 AF XY: 0.358 AC XY: 210301 AN XY: 587752

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.361

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.309 AC: 46927 AN: 152022 Hom.: 8420 Cov.: 31 AF XY: 0.315 AC XY: 23372 AN XY: 74306

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.313

Alfa AF: 0.353 Hom.: 11836

Bravo AF: 0.309

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.74

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: rs12850; hg19: chr7-127950725; COSMIC: COSV56162708; COSMIC: COSV56162708;