Genetic Variant MCF2L:c.2062-403A>G (chr13-113084489-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000535094.7(MCF2L):c.2062-403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 305,342 control chromosomes in the GnomAD database, including 60,151 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 0.61 ( 29006 hom., cov: 34)

Exomes 𝑓: 0.63 ( 31145 hom. )

Consequence

MCF2L
ENST00000535094.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.57

Publications

3 publications found

Variant links:

Genes affected

MCF2L (HGNC:14576): (MCF.2 cell line derived transforming sequence like) This gene encodes a guanine nucleotide exchange factor that interacts specifically with the GTP-bound Rac1 and plays a role in the Rho/Rac signaling pathways. A variant in this gene was associated with osteoarthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

MCF2L 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=-1.13).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535094.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MCF2L	NM_001112732.3	MANE Select	c.2062-403A>G	intron	N/A	NP_001106203.2
MCF2L	NM_001438390.1		c.2161-403A>G	intron	N/A	NP_001425319.1
MCF2L	NM_001438391.1		c.2152-403A>G	intron	N/A	NP_001425320.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MCF2L	ENST00000535094.7	TSL:2 MANE Select	c.2062-403A>G	intron	N/A	ENSP00000440374.2
MCF2L	ENST00000421756.5	TSL:1	c.2074-403A>G	intron	N/A	ENSP00000397285.1
MCF2L	ENST00000375597.8	TSL:1	c.2056-403A>G	intron	N/A	ENSP00000364747.4

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

93121

AN:

152080

Hom.:

28995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.664

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.638

GnomAD4 exome

AF:

0.629

AC:

96318

AN:

153144

Hom.:

31145

AF XY:

0.627

AC XY:

48893

AN XY:

77994

show subpopulations

African (AFR)

AF:

0.479

AC:

2507

AN:

5238

American (AMR)

AF:

0.539

AC:

3327

AN:

6172

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

3454

AN:

5122

East Asian (EAS)

AF:

0.460

AC:

4706

AN:

10240

South Asian (SAS)

AF:

0.585

AC:

6621

AN:

11326

European-Finnish (FIN)

AF:

0.653

AC:

5357

AN:

8204

Middle Eastern (MID)

AF:

0.616

AC:

440

AN:

714

European-Non Finnish (NFE)

AF:

0.662

AC:

63990

AN:

96622

Other (OTH)

AF:

0.622

AC:

5916

AN:

9506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1656

3313

4969

6626

8282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.612

AC:

93161

AN:

152198

Hom.:

29006

Cov.:

AF XY:

0.611

AC XY:

45440

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.504

AC:

20944

AN:

41522

American (AMR)

AF:

0.587

AC:

8978

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

2421

AN:

3472

East Asian (EAS)

AF:

0.507

AC:

2628

AN:

5180

South Asian (SAS)

AF:

0.622

AC:

3001

AN:

4824

European-Finnish (FIN)

AF:

0.664

AC:

7032

AN:

10588

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.677

AC:

46013

AN:

68006

Other (OTH)

AF:

0.642

AC:

1358

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1878

3756

5634

7512

9390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.643

Hom.:

4146

Bravo

AF:

0.596

Asia WGS

AF:

0.566

AC:

1966

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.39

(source)

DANN

Benign

0.31

PhyloP100

-3.6

Mutation Taster

=100/0

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

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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