1-145925774-G-A

Position:

• chr1-145925774-G-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.*108C>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 0.00186 in 1,305,520 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (3 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (13 hom.)
• Consequence: RBM8A NM_005105.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0360

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]

ENSG00000289565 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-145925774-G-A is Benign according to our data. Variant chr1-145925774-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1199622.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 = 0.00509 (775/152222) while in subpopulation AFR AF= 0.0153 (637/41500). AF 95% confidence interval is 0.0144. There are 3 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM8A	NM_005105.5	c.*108C>T		3_prime_UTR_variant	6/6	ENST00000583313.7	NP_005096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM8A	ENST00000583313	c.*108C>T		3_prime_UTR_variant	6/6	1	NM_005105.5	ENSP00000463058.2
ENSG00000289565	ENST00000632040.1	n.*19+89C>T		intron_variant		2		ENSP00000488887.1

Frequencies

GnomAD3 genomes AF: 0.00499 AC: 759 AN: 152104 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00143 AC: 1651 AN: 1153298 Hom.: 13 Cov.: 16 AF XY: 0.00162 AC XY: 948 AN XY: 584606

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.00135

Gnomad4 ASJ exome AF: 0.00266

Gnomad4 EAS exome AF: 0.00292

Gnomad4 SAS exome AF: 0.00746

Gnomad4 FIN exome AF: 0.0000778

Gnomad4 NFE exome AF: 0.000388

Gnomad4 OTH exome AF: 0.00273

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152222 Hom.: 3 Cov.: 30 AF XY: 0.00500 AC XY: 372 AN XY: 74418

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00402 Hom.: 1

Bravo AF: 0.00521

Asia WGS AF: 0.00953 AC: 33 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.72
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13275; hg19: chr1-145509319;