chr7-128310672-G-A

Variant names:

• chr7-128310672-G-A
• rs12850
• NM_018077.3:c.*125C>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.*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
• Publications: 15 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=-0.85).
• 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 rank	MANE	Protein	UniProt
RBM28	NM_018077.3	c.*125C>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2	c.*125C>T		3_prime_UTR_variant	Exon 15 of 15		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM28	ENST00000223073.6	c.*125C>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_018077.3	ENSP00000223073.1
RBM28	ENST00000481788.1	n.777C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3
RBM28	ENST00000415472.6	c.*125C>T		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000390517.2

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

African (AFR) AF: 0.121 AC: 3307 AN: 27328

American (AMR) AF: 0.547 AC: 24132 AN: 44090

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 8470 AN: 24128

East Asian (EAS) AF: 0.595 AC: 22786 AN: 38304

South Asian (SAS) AF: 0.337 AC: 26713 AN: 79382

European-Finnish (FIN) AF: 0.361 AC: 14504 AN: 40132

Middle Eastern (MID) AF: 0.300 AC: 1553 AN: 5174

European-Non Finnish (NFE) AF: 0.349 AC: 294114 AN: 843450

Other (OTH) AF: 0.353 AC: 17869 AN: 50636

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

African (AFR) AF: 0.133 AC: 5534 AN: 41490

American (AMR) AF: 0.437 AC: 6675 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3066 AN: 5142

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10562

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23747 AN: 67966

Other (OTH) AF: 0.313 AC: 659 AN: 2108

Alfa AF: 0.348 Hom.: 32028

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
PhyloP100		-0.63
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: rs12850; hg19: chr7-127950725; COSMIC: COSV56162708; COSMIC: COSV56162708;