rs1130329

Variant names:

• chr7-5072923-A-C
• rs1130329
• ENST00000407184.5:c.437A>C
• RBAK-RBAKDN p.Glu146Ala

Variant summary

Our verdict is Benign. The variant received -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. 14/17 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
• Publications: 17 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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
	RBAK-RBAKDN	NM_001204513.3		c.*34A>C		splice_region	Exon 6 of 6	NP_001191442.1	A0A0A6YYG8
	RBAK-RBAKDN	NM_001204513.3		c.*34A>C		3_prime_UTR	Exon 6 of 6	NP_001191442.1	A0A0A6YYG8
	RBAKDN	NR_015343.2		n.279A>C		splice_region non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.437A>C	p.Glu146Ala	missense splice_region	Exon 8 of 8	ENSP00000385560.1	I3L0D1
	RBAKDN	ENST00000498308.2	TSL:1	c.120A>C	p.Gly40Gly	splice_region synonymous	Exon 3 of 3	ENSP00000520911.1	A0ABB0MVN3
	RBAK-RBAKDN	ENST00000396904.2	TSL:4	c.*34A>C		splice_region	Exon 6 of 6	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

GnomAD2 exomes AF: 0.346 AC: 84731 AN: 245176 AF XY: 0.352

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 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

African (AFR) AF: 0.440 AC: 14674 AN: 33348

American (AMR) AF: 0.263 AC: 11692 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 9970 AN: 25850

East Asian (EAS) AF: 0.353 AC: 13978 AN: 39630

South Asian (SAS) AF: 0.458 AC: 39317 AN: 85830

European-Finnish (FIN) AF: 0.354 AC: 18716 AN: 52904

Middle Eastern (MID) AF: 0.443 AC: 2225 AN: 5024

European-Non Finnish (NFE) AF: 0.314 AC: 347841 AN: 1109338

Other (OTH) AF: 0.348 AC: 20890 AN: 60056

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

African (AFR) AF: 0.437 AC: 18125 AN: 41472

American (AMR) AF: 0.283 AC: 4327 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1693 AN: 5138

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3855 AN: 10596

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21913 AN: 67960

Other (OTH) AF: 0.369 AC: 781 AN: 2114

Alfa AF: 0.337 Hom.: 28185

Bravo AF: 0.355

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
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
PhyloP100		-0.096
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.27	T
Sift4G	Benign	0.097	T
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs1130329;

hg19: chr7-5112554;

COSMIC: COSV67760219;

COSMIC: COSV67760219;