4-40432696-GGCGGCTGCGGCC-G

Position:

• chr4-40432696-GGCGGCTGCGGCC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3 BP3 BP6_Moderate BS2

The NM_001098634.2(RBM47):​c.1485_1496del​(p.Ala499_Ala502del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,599,412 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (9 hom.)
• Consequence: RBM47 NM_001098634.2 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.37

Genes affected

RBM47 (HGNC:30358): (RNA binding motif protein 47) Enables RNA binding activity. Predicted to act upstream of or within cytidine to uridine editing and hematopoietic progenitor cell differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP3: Nonframeshift variant in repetitive region in NM_001098634.2
• BP6: Variant 4-40432696-GGCGGCTGCGGCC-G is Benign according to our data. Variant chr4-40432696-GGCGGCTGCGGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2654737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 324 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM47	NM_001098634.2	c.1485_1496del	p.Ala499_Ala502del	inframe_deletion	6/7	ENST00000295971.12	NP_001092104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM47	ENST00000295971.12	c.1485_1496del	p.Ala499_Ala502del	inframe_deletion	6/7	5	NM_001098634.2	ENSP00000295971	P1

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 324 AN: 151256 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000388

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00289

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00350

Gnomad OTH AF: 0.00193

GnomAD3 exomes AF: 0.00231 AC: 566 AN: 245136 Hom.: 2 AF XY: 0.00240 AC XY: 321 AN XY: 133528

Gnomad AFR exome AF: 0.000528

Gnomad AMR exome AF: 0.000815

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000169

Gnomad SAS exome AF: 0.00318

Gnomad FIN exome AF: 0.00167

Gnomad NFE exome AF: 0.00342

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00326 AC: 4714 AN: 1448036 Hom.: 9 AF XY: 0.00329 AC XY: 2368 AN XY: 720382

Gnomad4 AFR exome AF: 0.000576

Gnomad4 AMR exome AF: 0.000859

Gnomad4 ASJ exome AF: 0.0000771

Gnomad4 EAS exome AF: 0.00298

Gnomad4 SAS exome AF: 0.00315

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00365

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00214 AC: 324 AN: 151376 Hom.: 1 Cov.: 32 AF XY: 0.00188 AC XY: 139 AN XY: 73948

Gnomad4 AFR AF: 0.000387

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00289

Gnomad4 NFE AF: 0.00350

Gnomad4 OTH AF: 0.00191

Alfa AF: 0.000501 Hom.: 0

Bravo AF: 0.00212

EpiCase AF: 0.00278

EpiControl AF: 0.00303

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

RBM47: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs528269773; hg19: chr4-40434713;