rs1405076109

Variant names:

• chr1-145923295-AC-A
• rs1405076109
• NM_005105.5:c.*2586delG

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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:):

GNRHR2 (HGNC:16341): (gonadotropin releasing hormone receptor 2 (pseudogene)) In non-hominoid primates and non-mammalian vertebrates, the gonadotropin releasing hormone 2 receptor gene (GnRHR2) encodes a seven-transmembrane G-protein coupled receptor. However, in human, the corresponding reading frame contains a premature stop codon, which has been suggested to encode a selenocysteine residue, but there is no solid evidence for selenocysteine incorporation (PMID: 12538601). It appears that the human GnRHR2 transcription occurs but the gene does not likely produce a functional multi-transmembrane protein. A non-transcribed pseudogene of GnRHR2 is located on chromosome 14. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RBM8A	NM_005105.5	c.*2586delG		3_prime_UTR_variant	Exon 6 of 6	ENST00000583313.7	NP_005096.1
GNRHR2	NR_002328.4	n.889-859delC		intron_variant	Intron 1 of 2
GNRHR2	NR_104033.1	n.298-859delC		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM8A	ENST00000583313.7	c.*2586delG		3_prime_UTR_variant	Exon 6 of 6	1	NM_005105.5	ENSP00000463058.2
ENSG00000289565	ENST00000632040.1	n.*19+2567delG		intron_variant	Intron 3 of 4	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.300 AC: 12195 AN: 40680

American (AMR) AF: 0.166 AC: 2524 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3470

East Asian (EAS) AF: 0.156 AC: 805 AN: 5154

South Asian (SAS) AF: 0.166 AC: 791 AN: 4778

European-Finnish (FIN) AF: 0.0593 AC: 623 AN: 10514

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0412 AC: 2797 AN: 67916

Other (OTH) AF: 0.121 AC: 254 AN: 2100

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1405076109; hg19: chr1-145511797;