Genetic Variant MIEN1:c.*392G>A (chr17-39729130-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Variant links:

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]

MIEN1 links:

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]

ERBB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEN1	NM_032339.5 link	c.*392G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000394231.8	NP_115715.3	Q9BRT3
MIEN1	NM_001330206.2 link	c.*468G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001317135.1	Q9BRT3J3KTI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEN1	ENST00000394231 link	c.*392G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_032339.5	ENSP00000377778.3		Q9BRT3

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4232

AN:

152092

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0280

AC XY:

994

AN XY:

35490

show subpopulations

Gnomad4 AFR exome

AF:

0.00557

AC:

AN:

1976

Gnomad4 AMR exome

AF:

0.0259

AC:

104

AN:

4012

Gnomad4 ASJ exome

AF:

0.0100

AC:

AN:

1894

Gnomad4 EAS exome

AF:

0.00136

AC:

AN:

4404

Gnomad4 SAS exome

AF:

0.0170

AC:

152

AN:

8960

Gnomad4 FIN exome

AF:

0.0528

AC:

102

AN:

1932

Gnomad4 NFE exome

AF:

0.0365

AC:

1476

AN:

40448

Gnomad4 Remaining exome

AF:

0.0289

AC:

105

AN:

3638

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0278

AC:

4232

AN:

152210

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2035

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00729

AC:

0.00729453

AN:

0.00729453

Gnomad4 AMR

AF:

0.0200

AC:

0.0199503

AN:

0.0199503

Gnomad4 ASJ

AF:

0.0107

AC:

0.0106751

AN:

0.0106751

Gnomad4 EAS

AF:

0.00116

AC:

0.00116009

AN:

0.00116009

Gnomad4 SAS

AF:

0.0174

AC:

0.0174491

AN:

0.0174491

Gnomad4 FIN

AF:

0.0515

AC:

0.0515192

AN:

0.0515192

Gnomad4 NFE

AF:

0.0424

AC:

0.0423711

AN:

0.0423711

Gnomad4 OTH

AF:

0.0237

AC:

0.0236742

AN:

0.0236742

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0368

Hom.:

294

Bravo

AF:

0.0239

Asia WGS

AF:

0.00491

AC:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over