rs1130329

Positions:

• chr7-5072923-A-C

Variant summary

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

The ENST00000407184.5(RBAK-RBAKDN):​c.437A>C​(p.Glu146Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,608,512 control chromosomes in the GnomAD database, including 91,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10161 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80983 hom.)
• Consequence: RBAK-RBAKDN ENST00000407184.5 missense, splice_region
• Scores: Splicing: ADA: 0.0009329
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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]

RBAKDN (HGNC:33770): (RBAK downstream neighbor)

RBAKDN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2622943E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBAK-RBAKDN	NM_001204513.3	c.*34A>C		splice_region_variant	6/6		NP_001191442.1
RBAK-RBAKDN	NM_001204513.3	c.*34A>C		3_prime_UTR_variant	6/6		NP_001191442.1
RBAKDN	NR_015343.2	n.279A>C		splice_region_variant, non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBAK-RBAKDN	ENST00000407184.5	c.437A>C	p.Glu146Ala	missense_variant, splice_region_variant	8/8	2		ENSP00000385560.1
RBAKDN	ENST00000498308.1	n.214A>C		splice_region_variant, non_coding_transcript_exon_variant	3/3	1		ENSP00000520911.1
RBAK-RBAKDN	ENST00000396904.2	c.*34A>C		splice_region_variant	6/6	4		ENSP00000380112.2
RBAK-RBAKDN	ENST00000396904.2	c.*34A>C		3_prime_UTR_variant	6/6	4		ENSP00000380112.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54512 AN: 151950 Hom.: 10149 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.366

GnomAD3 exomes AF: 0.346 AC: 84731 AN: 245176 Hom.: 15143 AF XY: 0.352 AC XY: 46866 AN XY: 132978

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.329 AC: 479303 AN: 1456444 Hom.: 80983 Cov.: 41 AF XY: 0.333 AC XY: 241407 AN XY: 724018

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.359 AC: 54562 AN: 152068 Hom.: 10161 Cov.: 32 AF XY: 0.360 AC XY: 26750 AN XY: 74332

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.369

Alfa AF: 0.336 Hom.: 18470

Bravo AF: 0.355

TwinsUK AF: 0.319 AC: 1182

ALSPAC AF: 0.321 AC: 1239

ESP6500AA AF: 0.427 AC: 1881

ESP6500EA AF: 0.326 AC: 2805

ExAC AF: 0.349 AC: 42391

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.95
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.00023	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.27	T
Sift4G	Benign	0.097	T
Vest4		0.039
ClinPred		0.0023	T
GERP RS		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00093
dbscSNV1_RF	Benign	0.028
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: rs1130329; hg19: chr7-5112554; COSMIC: COSV67760219; COSMIC: COSV67760219;