rs1355244503

Variant names:

• chr1-145923296-C-A
• rs1355244503
• NM_005105.5:c.*2586G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005105.5(RBM8A):​c.*2586G>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 0.0047 in 107,688 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0047 (2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.593).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0047 (506/107688) while in subpopulation AFR AF = 0.0179 (338/18880). AF 95% confidence interval is 0.0163. There are 2 homozygotes in GnomAd4. There are 254 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005105.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	NM_005105.5	MANE Select	c.*2586G>T		3_prime_UTR	Exon 6 of 6	NP_005096.1
	GNRHR2	NR_002328.4		n.889-859C>A		intron	N/A
	GNRHR2	NR_104033.1		n.298-859C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	ENST00000583313.7	TSL:1 MANE Select	c.*2586G>T		3_prime_UTR	Exon 6 of 6	ENSP00000463058.2
	GNRHR2	ENST00000312753.9	TSL:1	n.889-859C>A		intron	N/A
	GNRHR2	ENST00000361928.2	TSL:1	n.298-859C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 501 AN: 107666 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.00416

Gnomad FIN AF: 0.00243

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000859

Gnomad OTH AF: 0.00333

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

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: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00470 AC: 506 AN: 107688 Hom.: 2 Cov.: 29 AF XY: 0.00491 AC XY: 254 AN XY: 51754

African (AFR) AF: 0.0179 AC: 338 AN: 18880

American (AMR) AF: 0.00465 AC: 46 AN: 9894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2984

East Asian (EAS) AF: 0.00988 AC: 35 AN: 3542

South Asian (SAS) AF: 0.00385 AC: 12 AN: 3116

European-Finnish (FIN) AF: 0.00243 AC: 18 AN: 7396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.000859 AC: 51 AN: 59344

Other (OTH) AF: 0.00396 AC: 6 AN: 1514

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.59
PhyloP100		-1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1355244503;