7-4993918-T-G

Position:

• chr7-4993918-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000407184.5(RBAK-RBAKDN):​c.-45+8843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 623,140 control chromosomes in the GnomAD database, including 101,796 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29089 hom., cov: 33)
  • Exomes 𝑓: 0.55 (72707 hom.)
• Consequence: RBAK-RBAKDN ENST00000407184.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

RBAK-RBAKDN (HGNC:42971): (RBAK-RBAKDN readthrough) This locus represents naturally occurring read-through transcription between the neighboring RBAK (RB-associated KRAB zinc finger) and LOC389458 (hypothetical LOC389458) genes on chromosome 7. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Mar 2011]

RNF216P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF216P1	NR_015449.1	n.698-2692T>G		intron_variant
RNF216P1	NR_023384.1	n.763-1557T>G		intron_variant
RNF216P1	NR_023385.1	n.583-2692T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBAK-RBAKDN	ENST00000407184.5	c.-45+8843T>G		intron_variant		2		ENSP00000385560.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92534 AN: 152086 Hom.: 29043 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.550 AC: 258991 AN: 470934 Hom.: 72707 Cov.: 7 AF XY: 0.549 AC XY: 126735 AN XY: 230936

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.609 AC: 92640 AN: 152206 Hom.: 29089 Cov.: 33 AF XY: 0.612 AC XY: 45571 AN XY: 74432

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.593

Alfa AF: 0.450 Hom.: 1607

Bravo AF: 0.610

Asia WGS AF: 0.642 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.8
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6463213; hg19: chr7-5033549;