rs2233152

Variant names:

• chr19-40775111-G-A
• rs2233152
• ENST00000600729.2:n.-6-426G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-40775111-G-A
• chr19-40775111-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 38 publications found

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 (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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600729.2. 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
	MIA	NM_001202553.2		c.-107G>A		upstream_gene	N/A	NP_001189482.1	Q16674-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIA-RAB4B	ENST00000600729.2	TSL:5	n.-6-426G>A		intron	N/A	ENSP00000472384.1	W4VSR3
	MIA	ENST00000928258.1		c.-6-426G>A		intron	N/A	ENSP00000598317.1
	MIA	ENST00000597600.5	TSL:4	c.-6-426G>A		intron	N/A	ENSP00000472982.1	M0R343

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18223 AN: 152020 Hom.: 1248 Cov.: 32

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

African (AFR) AF: 0.0488 AC: 20 AN: 410

American (AMR) AF: 0.143 AC: 395 AN: 2756

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 28 AN: 344

East Asian (EAS) AF: 0.0630 AC: 81 AN: 1286

South Asian (SAS) AF: 0.147 AC: 347 AN: 2356

European-Finnish (FIN) AF: 0.108 AC: 60 AN: 558

Middle Eastern (MID) AF: 0.0435 AC: 2 AN: 46

European-Non Finnish (NFE) AF: 0.125 AC: 1488 AN: 11908

Other (OTH) AF: 0.119 AC: 126 AN: 1060

GnomAD4 genome AF: 0.120 AC: 18247 AN: 152140 Hom.: 1252 Cov.: 32 AF XY: 0.121 AC XY: 8992 AN XY: 74378

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: 36 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9853 AN: 67972

Other (OTH) AF: 0.113 AC: 239 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.76
PhyloP100		1.8
PromoterAI		0.023	Neutral

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

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

Other links and lift over

dbSNP: rs2233152;

hg19: chr19-41281016;