rs1355244503

Positions:

• chr1-145923296-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

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

Ensembl

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

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.00465

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00988

Gnomad4 SAS AF: 0.00385

Gnomad4 FIN AF: 0.00243

Gnomad4 NFE AF: 0.000859

Gnomad4 OTH AF: 0.00396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1355244503; hg19: -;