rs4252665

Positions:

• chr17-39729130-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032339.5(MIEN1):​c.*392G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 219,790 control chromosomes in the GnomAD database, including 134 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 0.028 (87 hom., cov: 32)
  • Exomes 𝑓: 0.029 (47 hom.)
• Consequence: MIEN1 NM_032339.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

Genes affected

MIEN1 (HGNC:28230): (migration and invasion enhancer 1) Involved in negative regulation of apoptotic process; positive regulation of cell migration; and positive regulation of filopodium assembly. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. Is intrinsic component of the cytoplasmic side of the plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERBB2 (HGNC:3430): (erb-b2 receptor tyrosine kinase 2) This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0278 (4232/152210) while in subpopulation NFE AF= 0.0424 (2882/68018). AF 95% confidence interval is 0.0411. There are 87 homozygotes in gnomad4. There are 2035 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEN1	NM_032339.5	c.*392G>A		3_prime_UTR_variant	4/4	ENST00000394231.8	NP_115715.3
MIEN1	NM_001330206.2	c.*468G>A		3_prime_UTR_variant	3/3		NP_001317135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEN1	ENST00000394231.8	c.*392G>A		3_prime_UTR_variant	4/4	1	NM_032339.5	ENSP00000377778	P1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4232 AN: 152092 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00732

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0292 AC: 1976 AN: 67580 Hom.: 47 Cov.: 0 AF XY: 0.0280 AC XY: 994 AN XY: 35490

Gnomad4 AFR exome AF: 0.00557

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0100

Gnomad4 EAS exome AF: 0.00136

Gnomad4 SAS exome AF: 0.0170

Gnomad4 FIN exome AF: 0.0528

Gnomad4 NFE exome AF: 0.0365

Gnomad4 OTH exome AF: 0.0289

GnomAD4 genome AF: 0.0278 AC: 4232 AN: 152210 Hom.: 87 Cov.: 32 AF XY: 0.0274 AC XY: 2035 AN XY: 74400

Gnomad4 AFR AF: 0.00729

Gnomad4 AMR AF: 0.0200

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0368 Hom.: 105

Bravo AF: 0.0239

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4252665; hg19: chr17-37885383;