Genetic Variant MCF2:c.1543+91G>A (chrX-139614790-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001171876.2(MCF2):c.1543+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 841,890 control chromosomes in the GnomAD database, including 1,043 homozygotes. There are 5,600 hemizygotes in GnomAD. 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 0.022 ( 99 hom., 819 hem., cov: 23)

Exomes 𝑓: 0.021 ( 944 hom. 4781 hem. )

Consequence

MCF2
NM_001171876.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0970

Publications

0 publications found

Variant links:

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

MCF2 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171876.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCF2	NM_001171876.2	MANE Select	c.1543+91G>A	intron	N/A	NP_001165347.1	P10911-5
MCF2	NM_001099855.2		c.1543+91G>A	intron	N/A	NP_001093325.1	P10911-3
MCF2	NM_001171879.2		c.1363+91G>A	intron	N/A	NP_001165350.1	P10911-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCF2	ENST00000519895.6	TSL:2 MANE Select	c.1543+91G>A	intron	N/A	ENSP00000430276.1	P10911-5
MCF2	ENST00000338585.6	TSL:1	c.1363+91G>A	intron	N/A	ENSP00000342204.6	P10911-4
MCF2	ENST00000370576.9	TSL:1	c.1363+91G>A	intron	N/A	ENSP00000359608.4	P10911-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

2428

AN:

110853

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00409

Gnomad AMI

AF:

0.0234

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.00342

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.0333

Gnomad FIN

AF:

0.0383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.0399

GnomAD4 exome

AF:

0.0213

AC:

15592

AN:

730984

Hom.:

944

AF XY:

0.0248

AC XY:

4781

AN XY:

192748

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

17840

American (AMR)

AF:

0.189

AC:

4382

AN:

23233

Ashkenazi Jewish (ASJ)

AF:

0.00381

AC:

AN:

13640

East Asian (EAS)

AF:

0.223

AC:

6232

AN:

27989

South Asian (SAS)

AF:

0.0351

AC:

1308

AN:

37265

European-Finnish (FIN)

AF:

0.0390

AC:

1473

AN:

37799

Middle Eastern (MID)

AF:

0.00632

AC:

AN:

2849

European-Non Finnish (NFE)

AF:

0.00258

AC:

1387

AN:

537222

Other (OTH)

AF:

0.0210

AC:

695

AN:

33147

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

483

966

1448

1931

2414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.0220

AC:

2438

AN:

110906

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

819

AN XY:

33262

show subpopulations

African (AFR)

AF:

0.00408

AC:

125

AN:

30643

American (AMR)

AF:

0.113

AC:

1172

AN:

10354

Ashkenazi Jewish (ASJ)

AF:

0.00342

AC:

AN:

2630

East Asian (EAS)

AF:

0.162

AC:

566

AN:

3496

South Asian (SAS)

AF:

0.0331

AC:

AN:

2632

European-Finnish (FIN)

AF:

0.0383

AC:

226

AN:

5898

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00337

AC:

178

AN:

52831

Other (OTH)

AF:

0.0388

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0134

Hom.:

Bravo

AF:

0.0356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

(source)

DANN

Benign

0.56

PhyloP100

0.097

PromoterAI

0.0033

Neutral

(source)

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