chr1-145925774-G-A

Variant names:

• chr1-145925774-G-A
• rs13275
• NM_005105.5:c.*108C>T

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.*108C>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 0.00186 in 1,305,520 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (3 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (13 hom.)
• Consequence: RBM8A NM_005105.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0360
• 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]

RBM8A Gene-Disease associations (from GenCC):

• thrombocytopenia-absent radius syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ENSG00000289565 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-145925774-G-A is Benign according to our data. Variant chr1-145925774-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1199622.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 = 0.00509 (775/152222) while in subpopulation AFR AF = 0.0153 (637/41500). AF 95% confidence interval is 0.0144. There are 3 homozygotes in GnomAd4. There are 372 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.*108C>T		3_prime_UTR	Exon 6 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.*108C>T		3_prime_UTR	Exon 6 of 6	ENSP00000463058.2	Q9Y5S9-1
	RBM8A	ENST00000369307.4	TSL:1	c.*108C>T		3_prime_UTR	Exon 6 of 6	ENSP00000358313.3	Q9Y5S9-2
	ENSG00000289565	ENST00000632040.1	TSL:2	n.*19+89C>T		intron	N/A	ENSP00000488887.1	A0A0J9YW13

Frequencies

GnomAD3 genomes AF: 0.00499 AC: 759 AN: 152104 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00143 AC: 1651 AN: 1153298 Hom.: 13 Cov.: 16 AF XY: 0.00162 AC XY: 948 AN XY: 584606

African (AFR) AF: 0.0135 AC: 358 AN: 26430

American (AMR) AF: 0.00135 AC: 55 AN: 40600

Ashkenazi Jewish (ASJ) AF: 0.00266 AC: 63 AN: 23646

East Asian (EAS) AF: 0.00292 AC: 110 AN: 37728

South Asian (SAS) AF: 0.00746 AC: 581 AN: 77918

European-Finnish (FIN) AF: 0.0000778 AC: 4 AN: 51440

Middle Eastern (MID) AF: 0.00456 AC: 16 AN: 3512

European-Non Finnish (NFE) AF: 0.000388 AC: 327 AN: 841922

Other (OTH) AF: 0.00273 AC: 137 AN: 50102

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152222 Hom.: 3 Cov.: 30 AF XY: 0.00500 AC XY: 372 AN XY: 74418

African (AFR) AF: 0.0153 AC: 637 AN: 41500

American (AMR) AF: 0.00118 AC: 18 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00443 AC: 23 AN: 5192

South Asian (SAS) AF: 0.00933 AC: 45 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

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

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68034

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00402 Hom.: 1

Bravo AF: 0.00521

Asia WGS AF: 0.00953 AC: 33 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		-0.036
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

Splicing

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

Other links and lift over

dbSNP: rs13275; hg19: chr1-145509319;