dbSNP rs2233152: MIA-RAB4B:n.-6-426G>A (chr19-40775111-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000600729.2(MIA-RAB4B):n.-6-426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 172,864 control chromosomes in the GnomAD database, including 1,445 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 0.12 ( 1252 hom., cov: 32)

Exomes 𝑓: 0.12 ( 193 hom. )

Consequence

MIA-RAB4B
ENST00000600729.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

38 publications found

Variant links:

Genes affected

MIA-RAB4B (HGNC:48352): (MIA-RAB4B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MIA (melanoma inhibitory activity) and RAB4B (RAB4B, member RAS oncogene family) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

MIA-RAB4B links:

MIA (HGNC:7076): (MIA SH3 domain containing) Predicted to enable growth factor activity. Predicted to be involved in extracellular matrix organization. Predicted to act upstream of or within cell-matrix adhesion. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

MIA links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA	NM_001202553.2 link	c.-107G>A		upstream_gene_variant			NP_001189482.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
MIA-RAB4B	ENST00000600729.2 link	n.-6-426G>A	intron_variant	Intron 1 of 10	5	ENSP00000472384.1
MIA	ENST00000597600.5 link	c.-6-426G>A	intron_variant	Intron 1 of 2	4	ENSP00000472982.1
MIA	ENST00000594436.5 link	c.-107G>A	upstream_gene_variant		2	ENSP00000470129.1
MIA	ENST00000597784.5 link	c.-205G>A	upstream_gene_variant		3	ENSP00000469499.1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18223

AN:

152020

Hom.:

1248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0703

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0782

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.123

AC:

2547

AN:

20724

Hom.:

193

AF XY:

0.126

AC XY:

1350

AN XY:

10692

show subpopulations

African (AFR)

AF:

0.0488

AC:

AN:

410

American (AMR)

AF:

0.143

AC:

395

AN:

2756

Ashkenazi Jewish (ASJ)

AF:

0.0814

AC:

AN:

344

East Asian (EAS)

AF:

0.0630

AC:

AN:

1286

South Asian (SAS)

AF:

0.147

AC:

347

AN:

2356

European-Finnish (FIN)

AF:

0.108

AC:

AN:

558

Middle Eastern (MID)

AF:

0.0435

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

1488

AN:

11908

Other (OTH)

AF:

0.119

AC:

126

AN:

1060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

214

320

427

534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.120

AC:

18247

AN:

152140

Hom.:

1252

Cov.:

AF XY:

0.121

AC XY:

8992

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0703

AC:

2920

AN:

41526

American (AMR)

AF:

0.136

AC:

2070

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

407

AN:

3472

East Asian (EAS)

AF:

0.0779

AC:

403

AN:

5170

South Asian (SAS)

AF:

0.170

AC:

820

AN:

4816

European-Finnish (FIN)

AF:

0.139

AC:

1469

AN:

10588

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.145

AC:

9853

AN:

67972

Other (OTH)

AF:

0.113

AC:

239

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

801

1603

2404

3206

4007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.134

Hom.:

6281

Bravo

AF:

0.114

Asia WGS

AF:

0.119

AC:

415

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

1.8

PromoterAI

0.023

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over