19-40775111-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000600729.2(MIA-RAB4B):​n.-6-426G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MIA-RAB4B ENST00000600729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs2233152; hg19: chr19-41281016;