rs139097271

Variant names:

• chr1-145926506-G-A
• rs139097271
• NM_005105.5:c.318C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-145926506-G-A
• chr1-145926506-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005105.5(RBM8A):​c.318C>T​(p.Leu106Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,614,078 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00046 (2 hom.)
• Consequence: RBM8A NM_005105.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.232
• Publications: 2 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]

ENSG00000289565 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-145926506-G-A is Benign according to our data. Variant chr1-145926506-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 436518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.232 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	NM_005105.5	MANE Select	c.318C>T	p.Leu106Leu	synonymous	Exon 4 of 6	NP_005096.1	Q9Y5S9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM8A	ENST00000583313.7	TSL:1 MANE Select	c.318C>T	p.Leu106Leu	synonymous	Exon 4 of 6	ENSP00000463058.2	Q9Y5S9-1
	RBM8A	ENST00000369307.4	TSL:1	c.315C>T	p.Leu105Leu	synonymous	Exon 4 of 6	ENSP00000358313.3	Q9Y5S9-2
	ENSG00000289565	ENST00000632040.1	TSL:2	n.111C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000488887.1	A0A0J9YW13

Frequencies

GnomAD3 genomes AF: 0.000782 AC: 119 AN: 152082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00717

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000811 AC: 204 AN: 251402 AF XY: 0.000729

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000464 AC: 678 AN: 1461878 Hom.: 2 Cov.: 31 AF XY: 0.000437 AC XY: 318 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00753 AC: 402 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000226 AC: 251 AN: 1112008

Other (OTH) AF: 0.000364 AC: 22 AN: 60394

GnomAD4 genome AF: 0.000782 AC: 119 AN: 152200 Hom.: 0 Cov.: 31 AF XY: 0.00102 AC XY: 76 AN XY: 74410

African (AFR) AF: 0.0000482 AC: 2 AN: 41532

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00717 AC: 76 AN: 10594

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000442 Hom.: 0

Bravo AF: 0.000159

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.72
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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: rs139097271; hg19: chr1-145508587; COSMIC: COSV57162902; COSMIC: COSV57162902;