chr1-145923295-AC-A

Position:

• chr1-145923295-AC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005105.5(RBM8A):​c.*2586delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,014 control chromosomes in the GnomAD database, including 2,207 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (2207 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM8A NM_005105.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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]

GNRHR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM8A	NM_005105.5	c.*2586delG		3_prime_UTR_variant	6/6	ENST00000583313.7	NP_005096.1
GNRHR2	NR_002328.4	n.889-859delC		intron_variant
GNRHR2	NR_104033.1	n.298-859delC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM8A	ENST00000583313	c.*2586delG		3_prime_UTR_variant	6/6	1	NM_005105.5	ENSP00000463058.2
ENSG00000289565	ENST00000632040.1	n.*19+2567delG		intron_variant		2		ENSP00000488887.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20226 AN: 150920 Hom.: 2203 Cov.: 29

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.120

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.134 AC: 20256 AN: 151014 Hom.: 2207 Cov.: 29 AF XY: 0.136 AC XY: 10069 AN XY: 73766

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1405076109; hg19: chr1-145511797;