rs2233152

Positions:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000597600.5(MIA):​c.-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 ENST00000597600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

Genes affected

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
MIA	NM_001202553.2			upstream_gene_variant			NP_001189482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA	ENST00000597600.5	c.-6-426G>A		intron_variant		4		ENSP00000472982

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

Gnomad4 AFR exome AF: 0.0488

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.0630

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.119

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

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.113

Alfa AF: 0.134 Hom.: 2964

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	20
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs2233152; hg19: chr19-41281016;