rs59285351

Variant names:

• chr1-145926947-G-T
• rs59285351
• NM_005105.5:c.128-61C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005105.5(RBM8A):​c.128-61C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,613,744 control chromosomes in the GnomAD database, including 4,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (2177 hom., cov: 30)
  • Exomes 𝑓: 0.014 (2067 hom.)
• Consequence: RBM8A NM_005105.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.717

Genes affected

RBM8A (HGNC:9905): (RNA binding motif protein 8A) This gene encodes a protein with a conserved RNA-binding motif. The protein is found predominantly in the nucleus, although it is also present in the cytoplasm. It is preferentially associated with mRNAs produced by splicing, including both nuclear mRNAs and newly exported cytoplasmic mRNAs. It is thought that the protein remains associated with spliced mRNAs as a tag to indicate where introns had been present, thus coupling pre- and post-mRNA splicing events. Previously, it was thought that two genes encode this protein, RBM8A and RBM8B; it is now thought that the RBM8B locus is a pseudogene. There are two alternate translation start codons with this gene, which result in two forms of the protein. An allele mutation and a low-frequency noncoding single-nucleotide polymorphism (SNP) in this gene cause thrombocytopenia-absent radius (TAR) syndrome. [provided by RefSeq, Jul 2013]

LIX1L-AS1 (HGNC:41210): (LIX1L antisense RNA 1)

ENSG00000289565 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-145926947-G-T is Benign according to our data. Variant chr1-145926947-G-T is described in ClinVar as [Benign]. Clinvar id is 167569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM8A	NM_005105.5	c.128-61C>A		intron_variant	Intron 2 of 5	ENST00000583313.7	NP_005096.1
LIX1L-AS1	NR_147182.1	n.116+1G>T		splice_donor_variant, intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM8A	ENST00000583313.7	c.128-61C>A		intron_variant	Intron 2 of 5	1	NM_005105.5	ENSP00000463058.2

Frequencies

GnomAD3 genomes AF: 0.0953 AC: 14456 AN: 151758 Hom.: 2163 Cov.: 30

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.0644

GnomAD4 exome AF: 0.0144 AC: 21081 AN: 1461868 Hom.: 2067 Cov.: 31 AF XY: 0.0145 AC XY: 10553 AN XY: 727236

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.0191

Gnomad4 SAS exome AF: 0.0521

Gnomad4 FIN exome AF: 0.0132

Gnomad4 NFE exome AF: 0.00147

Gnomad4 OTH exome AF: 0.0272

GnomAD4 genome AF: 0.0955 AC: 14510 AN: 151876 Hom.: 2177 Cov.: 30 AF XY: 0.0940 AC XY: 6976 AN XY: 74214

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.0302

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0144 Hom.: 192

Bravo AF: 0.105

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Feb 05, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.6
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs59285351; hg19: chr1-145508146;