NM_005105.5:c.206-20T>C

Variant names:

• chr1-145926638-A-G
• rs117017431
• NM_005105.5:c.206-20T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

The NM_005105.5(RBM8A):​c.206-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,792 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: RBM8A NM_005105.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.192
• 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 -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 1-145926638-A-G is Benign according to our data. Variant chr1-145926638-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1207363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0013 (198/152278) while in subpopulation EAS AF = 0.0275 (143/5192). AF 95% confidence interval is 0.0239. There are 1 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 28 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.206-20T>C		intron	N/A	NP_005096.1	Q9Y5S9-1
	LIX1L-AS1	NR_147182.1		n.-193A>G		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.206-20T>C		intron	N/A	ENSP00000463058.2	Q9Y5S9-1
	RBM8A	ENST00000369307.4	TSL:1	c.203-20T>C		intron	N/A	ENSP00000358313.3	Q9Y5S9-2
	RBM8A	ENST00000632555.1	TSL:3	c.206-20T>C		intron	N/A	ENSP00000488265.1	Q9Y5S9-1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152160 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00276 AC: 692 AN: 250790 AF XY: 0.00245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0297

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000985

GnomAD4 exome AF: 0.00112 AC: 1643 AN: 1461514 Hom.: 28 Cov.: 31 AF XY: 0.00109 AC XY: 790 AN XY: 727088

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.00302 AC: 135 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.0325 AC: 1289 AN: 39696

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5654

European-Non Finnish (NFE) AF: 0.0000764 AC: 85 AN: 1111868

Other (OTH) AF: 0.00151 AC: 91 AN: 60348

GnomAD4 genome AF: 0.00130 AC: 198 AN: 152278 Hom.: 1 Cov.: 31 AF XY: 0.00152 AC XY: 113 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.00281 AC: 43 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0275 AC: 143 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000890 Hom.: 0

Bravo AF: 0.00158

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.47
PhyloP100		-0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.64		Position offset: 1

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

Other links and lift over

dbSNP: rs117017431; hg19: chr1-145508455; COSMIC: COSV57162047; COSMIC: COSV57162047;