NM_021163.4:c.869A>C

Variant names:

• chr7-5064325-A-C
• rs368665058
• NM_021163.4:c.869A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_021163.4(RBAK):​c.869A>C​(p.Glu290Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: RBAK NM_021163.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.237
• Publications: 0 publications found

Genes affected

RBAK (HGNC:17680): (RB associated KRAB zinc finger) This gene encodes a nuclear protein which interacts with the tumor suppressor retinoblastoma 1. The two interacting proteins are thought to act as a transcriptional repressor for promoters which are activated by the E2F1 transcription factor. This protein contains a Kruppel-associated box (KRAB), which is a transcriptional repressor motif. Read-through transcripts that include exons from the downstream gene LOC389458 are expressed from this locus. [provided by RefSeq, Mar 2011]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049604654).
• BP6: Variant 7-5064325-A-C is Benign according to our data. Variant chr7-5064325-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3152047.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021163.4. 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
	RBAK	NM_021163.4	MANE Select	c.869A>C	p.Glu290Ala	missense	Exon 5 of 5	NP_066986.1	Q9NYW8-1
	RBAK	NM_001204456.2		c.869A>C	p.Glu290Ala	missense	Exon 6 of 6	NP_001191385.1	Q9NYW8-1
	RBAK-RBAKDN	NM_001204513.3		c.238+6546A>C		intron	N/A	NP_001191442.1	A0A0A6YYG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBAK	ENST00000396912.2	TSL:1 MANE Select	c.869A>C	p.Glu290Ala	missense	Exon 5 of 5	ENSP00000380120.1	Q9NYW8-1
	RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.299+570A>C		intron	N/A	ENSP00000385560.1	I3L0D1
	RBAK	ENST00000353796.7	TSL:2	c.869A>C	p.Glu290Ala	missense	Exon 6 of 6	ENSP00000275423.4	Q9NYW8-1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727210

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74386

African (AFR) AF: 0.000314 AC: 13 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000996 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00015	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.44	N
PhyloP100		-0.24
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.057
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.083
MVP		0.061
MPC		0.077
ClinPred		0.049	T
GERP RS		-4.3
Varity_R		0.075
gMVP		0.060
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs368665058; hg19: chr7-5103956;