Genetic Variant MINDY4:c.2226-1749G>C (chr7-30890208-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032222.3(MINDY4):c.2226-1749G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,212 control chromosomes in the GnomAD database, including 8,765 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 0.26 ( 8765 hom., cov: 33)

Consequence

MINDY4
NM_032222.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

2 publications found

Variant links:

Genes affected

MINDY4 (HGNC:21916): (MINDY lysine 48 deubiquitinase 4) Predicted to enable Lys48-specific deubiquitinase activity. Predicted to be involved in protein K48-linked deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

MINDY4 links:

ENSG00000250424 (HGNC:):

ENSG00000250424 links:

INMT-MINDY4 (HGNC:41995): (INMT-MINDY4 readthrough (NMD candidate)) This locus represents rare but naturally occurring read-through transcription between the INMT (indolethylamine N-methyltransferase) and FAM188B (family with sequence similarity 188, member B) genes on chromosome 7. The read-through transcript is unlikely to produce a protein because it is a nonsense-mediated mRNA decay (NMD) candidate based on translation from the supported INMT start codon. [provided by RefSeq, Nov 2010]

INMT-MINDY4 links:

OSBPL9P6 (HGNC:48736):

OSBPL9P6 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MINDY4	NM_032222.3 link	c.2226-1749G>C	intron_variant	Intron 17 of 17	ENST00000265299.6	NP_115598.2
OSBPL9P6		n.30890208G>C	intragenic_variant
INMT-MINDY4	NR_037598.1 link	n.2755-1749G>C	intron_variant	Intron 19 of 19

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MINDY4	ENST00000265299.6 link	c.2226-1749G>C	intron_variant	Intron 17 of 17	1	NM_032222.3	ENSP00000265299.6
ENSG00000250424	ENST00000509504.2 link	c.620+7215G>C	intron_variant	Intron 7 of 10	5		ENSP00000421315.2
INMT-MINDY4	ENST00000458257.5 link	n.*2313-1749G>C	intron_variant	Intron 19 of 19	2		ENSP00000456039.1
MINDY4	ENST00000409881.1 link	n.2059-1749G>C	intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39224

AN:

152094

Hom.:

8737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.0906

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.238

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

GnomAD4 genome

AF:

0.258

AC:

39312

AN:

152212

Hom.:

8765

Cov.:

AF XY:

0.257

AC XY:

19153

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.600

AC:

24891

AN:

41504

American (AMR)

AF:

0.134

AC:

2049

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

664

AN:

3466

East Asian (EAS)

AF:

0.319

AC:

1656

AN:

5184

South Asian (SAS)

AF:

0.338

AC:

1628

AN:

4822

European-Finnish (FIN)

AF:

0.0906

AC:

962

AN:

10618

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6824

AN:

68010

Other (OTH)

AF:

0.240

AC:

508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1155

2310

3466

4621

5776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.185

Hom.:

689

Bravo

AF:

0.273

Asia WGS

AF:

0.336

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.44

(source)

DANN

Benign

0.47

PhyloP100

0.063

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over