7-4993918-T-G

Variant names:

• chr7-4993918-T-G
• rs6463213
• ENST00000407184.5:c.-45+8843T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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:33610): (ring finger protein 216 pseudogene 1)

ENSG00000288633 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000407184.5. 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
	RNF216P1	NR_015449.1		n.698-2692T>G		intron	N/A
	RNF216P1	NR_023384.1		n.763-1557T>G		intron	N/A
	RNF216P1	NR_023385.1		n.583-2692T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.-45+8843T>G		intron	N/A	ENSP00000385560.1	I3L0D1
	RNF216P1	ENST00000403969.5	TSL:1	n.518-2692T>G		intron	N/A
	RNF216P1	ENST00000404006.5	TSL:1	n.646-2692T>G		intron	N/A

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

African (AFR) AF: 0.774 AC: 8460 AN: 10926

American (AMR) AF: 0.522 AC: 3784 AN: 7244

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 5293 AN: 10274

East Asian (EAS) AF: 0.774 AC: 17998 AN: 23242

South Asian (SAS) AF: 0.572 AC: 3609 AN: 6304

European-Finnish (FIN) AF: 0.608 AC: 18259 AN: 30016

Middle Eastern (MID) AF: 0.596 AC: 1012 AN: 1698

European-Non Finnish (NFE) AF: 0.524 AC: 187602 AN: 358270

Other (OTH) AF: 0.565 AC: 12974 AN: 22960

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

African (AFR) AF: 0.774 AC: 32141 AN: 41536

American (AMR) AF: 0.520 AC: 7965 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3562 AN: 5174

South Asian (SAS) AF: 0.583 AC: 2811 AN: 4820

European-Finnish (FIN) AF: 0.618 AC: 6545 AN: 10590

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35808 AN: 68004

Other (OTH) AF: 0.593 AC: 1249 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.8
DANN	Benign	0.59
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6463213;

hg19: chr7-5033549;