1-110341022-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_022768.5(RBM15):c.1617G>A(p.Gln539=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00126 in 1,614,226 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (11 hom.)
• Consequence: RBM15 NM_022768.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.49

Genes affected

RBM15 (HGNC:14959): (RNA binding motif protein 15) Members of the SPEN (Split-end) family of proteins, including RBM15, have repressor function in several signaling pathways and may bind to RNA through interaction with spliceosome components (Hiriart et al., 2005 [PubMed 16129689]).[supplied by OMIM, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-110341022-G-A is Benign according to our data. Variant chr1-110341022-G-A is described in ClinVar as [Benign]. Clinvar id is 775574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00674 (1027/152362) while in subpopulation AFR AF= 0.0229 (952/41584). AF 95% confidence interval is 0.0217. There are 11 homozygotes in gnomad4. There are 483 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1025 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM15	NM_022768.5	c.1617G>A	p.Gln539=	synonymous_variant	1/3	ENST00000369784.9
RBM15	NM_001201545.2	c.1617G>A	p.Gln539=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM15	ENST00000369784.9	c.1617G>A	p.Gln539=	synonymous_variant	1/3	1	NM_022768.5	A2

Frequencies

GnomAD3 genomes AF: 0.00673 AC: 1025 AN: 152244 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00184 AC: 462 AN: 251456 Hom.: 7 AF XY: 0.00130 AC XY: 176 AN XY: 135900

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000688 AC: 1006 AN: 1461864 Hom.: 11 Cov.: 34 AF XY: 0.000582 AC XY: 423 AN XY: 727224

Gnomad4 AFR exome AF: 0.0230

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000432

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00674 AC: 1027 AN: 152362 Hom.: 11 Cov.: 32 AF XY: 0.00648 AC XY: 483 AN XY: 74504

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00345 Hom.: 4

Bravo AF: 0.00761

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	7.6
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs61740988; hg19: chr1-110883644;