rs1534310

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000343023.10(MCM7):c.-252T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 802,682 control chromosomes in the GnomAD database, including 30,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5067 hom., cov: 33)

Exomes 𝑓: 0.27 ( 25554 hom. )

Consequence

MCM7
ENST00000343023.10 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.224

Publications

13 publications found

Variant links:

Genes affected

MCM7 (HGNC:6950): (minichromosome maintenance complex component 7) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MCM7 links:

AP4M1 (HGNC:574): (adaptor related protein complex 4 subunit mu 1) This gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system. [provided by RefSeq, Jul 2008]

AP4M1 Gene-Disease associations (from GenCC):

AP-4 deficiency syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 50
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
AP4-related intellectual disability and spastic paraplegia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AP4M1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 7-100101546-A-T is Benign according to our data. Variant chr7-100101546-A-T is described in ClinVar as Benign. ClinVar VariationId is 680067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000343023.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
AP4M1	NM_001438824.1	c.-7-162A>T	intron	N/A	NP_001425753.1
AP4M1	NM_001438825.1	c.-8+50A>T	intron	N/A	NP_001425754.1
AP4M1	NM_001438826.1	c.-7-162A>T	intron	N/A	NP_001425755.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCM7	ENST00000343023.10	TSL:1	c.-252T>A	5_prime_UTR	Exon 1 of 9	ENSP00000344006.6	P33993-2
MCM7	ENST00000489841.6	TSL:1	n.395T>A	non_coding_transcript_exon	Exon 1 of 14
AP4M1	ENST00000907395.1		c.-169A>T	5_prime_UTR	Exon 1 of 16	ENSP00000577454.1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38019

AN:

152034

Hom.:

5063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.274

AC:

178428

AN:

650528

Hom.:

25554

Cov.:

AF XY:

0.275

AC XY:

94657

AN XY:

344224

show subpopulations

African (AFR)

AF:

0.178

AC:

3068

AN:

17228

American (AMR)

AF:

0.212

AC:

6950

AN:

32708

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

4833

AN:

19532

East Asian (EAS)

AF:

0.379

AC:

12392

AN:

32678

South Asian (SAS)

AF:

0.287

AC:

18198

AN:

63336

European-Finnish (FIN)

AF:

0.307

AC:

11924

AN:

38848

Middle Eastern (MID)

AF:

0.162

AC:

422

AN:

2606

European-Non Finnish (NFE)

AF:

0.273

AC:

112016

AN:

410240

Other (OTH)

AF:

0.259

AC:

8625

AN:

33352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

7905

15811

23716

31622

39527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1680

3360

5040

6720

8400

<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:

0.250

AC:

38037

AN:

152154

Hom.:

5067

Cov.:

AF XY:

0.252

AC XY:

18749

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.182

AC:

7545

AN:

41530

American (AMR)

AF:

0.213

AC:

3254

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

858

AN:

3466

East Asian (EAS)

AF:

0.406

AC:

2097

AN:

5164

South Asian (SAS)

AF:

0.306

AC:

1476

AN:

4826

European-Finnish (FIN)

AF:

0.311

AC:

3291

AN:

10584

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18765

AN:

67980

Other (OTH)

AF:

0.232

AC:

490

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1491

2982

4473

5964

7455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.162

Hom.:

357

Bravo

AF:

0.239

Asia WGS

AF:

0.372

AC:

1295

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

(source)

DANN

Benign

0.86

PhyloP100

0.22

PromoterAI

0.0014

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over