NM_005105.5:c.205+17C>A

Variant names:

• chr1-145926792-G-T
• rs115417561
• NM_005105.5:c.205+17C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005105.5(RBM8A):​c.205+17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,006 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (10 hom.)
• Consequence: RBM8A NM_005105.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.201

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 1-145926792-G-T is Benign according to our data. Variant chr1-145926792-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1217054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00424 (645/152146) while in subpopulation AFR AF= 0.0128 (532/41496). AF 95% confidence interval is 0.0119. There are 5 homozygotes in gnomad4. There are 305 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM8A	NM_005105.5	c.205+17C>A		intron_variant	Intron 3 of 5	ENST00000583313.7	NP_005096.1
LIX1L-AS1	NR_147182.1	n.-39G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM8A	ENST00000583313.7	c.205+17C>A		intron_variant	Intron 3 of 5	1	NM_005105.5	ENSP00000463058.2
ENSG00000289565	ENST00000632040.1	n.-176C>A		upstream_gene_variant		2		ENSP00000488887.1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 646 AN: 152028 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00191 AC: 479 AN: 251440 Hom.: 5 AF XY: 0.00184 AC XY: 250 AN XY: 135896

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00454

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00108 AC: 1578 AN: 1461860 Hom.: 10 Cov.: 31 AF XY: 0.00114 AC XY: 829 AN XY: 727236

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00377

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000509

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00424 AC: 645 AN: 152146 Hom.: 5 Cov.: 31 AF XY: 0.00410 AC XY: 305 AN XY: 74364

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.00482

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Radial aplasia-thrombocytopenia syndrome Benign:2

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 06, 2020

GeneDx

Significance: Likely 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	4.2
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs115417561; hg19: chr1-145508301;