1-145926792-G-T

Variant names:

• chr1-145926792-G-T
• rs115417561
• NM_005105.5:c.205+17C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005105.5(RBM8A):​c.205+17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,614,006 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (10 hom.)
• Consequence: RBM8A NM_005105.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.201
• Publications: 1 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]

LIX1L-AS1 (HGNC:41210): (LIX1L antisense RNA 1)

ENSG00000289565 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-145926792-G-T is Benign according to our data. Variant chr1-145926792-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1217054.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 = 0.00424 (645/152146) while in subpopulation AFR AF = 0.0128 (532/41496). AF 95% confidence interval is 0.0119. There are 5 homozygotes in GnomAd4. There are 305 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	NM_005105.5	MANE Select	c.205+17C>A		intron	N/A	NP_005096.1	Q9Y5S9-1
	LIX1L-AS1	NR_147182.1		n.-39G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	ENST00000583313.7	TSL:1 MANE Select	c.205+17C>A		intron	N/A	ENSP00000463058.2	Q9Y5S9-1
	RBM8A	ENST00000369307.4	TSL:1	c.202+17C>A		intron	N/A	ENSP00000358313.3	Q9Y5S9-2
	RBM8A	ENST00000632555.1	TSL:3	c.205+17C>A		intron	N/A	ENSP00000488265.1	Q9Y5S9-1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 646 AN: 152028 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00191 AC: 479 AN: 251440 AF XY: 0.00184

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00108 AC: 1578 AN: 1461860 Hom.: 10 Cov.: 31 AF XY: 0.00114 AC XY: 829 AN XY: 727236

African (AFR) AF: 0.0153 AC: 512 AN: 33478

American (AMR) AF: 0.00121 AC: 54 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00377 AC: 325 AN: 86254

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53420

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000509 AC: 566 AN: 1111992

Other (OTH) AF: 0.00162 AC: 98 AN: 60390

GnomAD4 genome AF: 0.00424 AC: 645 AN: 152146 Hom.: 5 Cov.: 31 AF XY: 0.00410 AC XY: 305 AN XY: 74364

African (AFR) AF: 0.0128 AC: 532 AN: 41496

American (AMR) AF: 0.00242 AC: 37 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4818

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 67990

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.000508 Hom.: 0

Bravo AF: 0.00482

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Radial aplasia-thrombocytopenia syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.2
DANN	Benign	0.86
PhyloP100		-0.20
PromoterAI		0.026	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -2

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

Other links and lift over

dbSNP: rs115417561; hg19: chr1-145508301;