Variant rs4875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001369783.1(MLF1):c.615T>C(p.Ser205=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,610,636 control chromosomes in the GnomAD database, including 235,459 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.58 ( 25971 hom., cov: 31)

Exomes 𝑓: 0.53 ( 209488 hom. )

Consequence

MLF1
NM_001369783.1 splice_region, synonymous

Scores

Splicing: ADA: 0.004298

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

MLF1 (HGNC:7125): (myeloid leukemia factor 1) This gene encodes an oncoprotein which is thought to play a role in the phenotypic determination of hemopoetic cells. Translocations between this gene and nucleophosmin have been associated with myelodysplastic syndrome and acute myeloid leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2010]

MLF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-158602808-T-C is Benign according to our data. Variant chr3-158602808-T-C is described in ClinVar as [Benign]. Clinvar id is 3059532.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-158602808-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLF1	NM_001369783.1 linkuse as main transcript	c.615T>C	p.Ser205=	splice_region_variant, synonymous_variant	7/8	ENST00000466246.7	NP_001356712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLF1	ENST00000466246.7 linkuse as main transcript	c.615T>C	p.Ser205=	splice_region_variant, synonymous_variant	7/8	2	NM_001369783.1	ENSP00000417278

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87398

AN:

151842

Hom.:

25929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.538

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.553

GnomAD3 exomes

AF:

0.540

AC:

135143

AN:

250350

Hom.:

37281

AF XY:

0.540

AC XY:

73008

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.723

Gnomad AMR exome

AF:

0.568

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.515

Gnomad NFE exome

AF:

0.533

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.533

AC:

777426

AN:

1458676

Hom.:

209488

Cov.:

AF XY:

0.534

AC XY:

387831

AN XY:

725724

show subpopulations

Gnomad4 AFR exome

AF:

0.729

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.517

Gnomad4 EAS exome

AF:

0.350

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.514

Gnomad4 NFE exome

AF:

0.529

Gnomad4 OTH exome

AF:

0.537

GnomAD4 genome

AF:

0.576

AC:

87492

AN:

151960

Hom.:

25971

Cov.:

AF XY:

0.576

AC XY:

42784

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.719

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.507

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.527

Gnomad4 OTH

AF:

0.556

Alfa

AF:

0.534

Hom.:

48564

Bravo

AF:

0.582

Asia WGS

AF:

0.532

AC:

1851

AN:

3478

EpiCase

AF:

0.535

EpiControl

AF:

0.540

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MLF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.8

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0043

dbscSNV1_RF

Benign

0.14

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over