Variant X-139596585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001171876.2(MCF2):c.2469C>T(p.Asp823=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,208,139 control chromosomes in the GnomAD database, including 499 homozygotes. There are 8,169 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 116 hom., 1300 hem., cov: 23)

Exomes 𝑓: 0.019 ( 383 hom. 6869 hem. )

Consequence

MCF2
NM_001171876.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.153

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-139596585-G-A is Benign according to our data. Variant chrX-139596585-G-A is described in ClinVar as [Benign]. Clinvar id is 1294008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-139596585-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2 linkuse as main transcript	c.2469C>T	p.Asp823=	synonymous_variant	23/29	ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6 linkuse as main transcript	c.2469C>T	p.Asp823=	synonymous_variant	23/29	2	NM_001171876.2	P4	P10911-5

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

4555

AN:

111641

Hom.:

116

Cov.:

AF XY:

0.0381

AC XY:

1291

AN XY:

33893

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.0206

Gnomad MID

AF:

0.0335

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0336

AC:

6151

AN:

182886

Hom.:

151

AF XY:

0.0298

AC XY:

2010

AN XY:

67518

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.0615

Gnomad ASJ exome

AF:

0.00401

Gnomad EAS exome

AF:

0.0857

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.0208

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0193

AC:

21211

AN:

1096445

Hom.:

383

Cov.:

AF XY:

0.0190

AC XY:

6869

AN XY:

362149

show subpopulations

Gnomad4 AFR exome

AF:

0.0904

Gnomad4 AMR exome

AF:

0.0649

Gnomad4 ASJ exome

AF:

0.00501

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0309

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0408

AC:

4559

AN:

111694

Hom.:

116

Cov.:

AF XY:

0.0383

AC XY:

1300

AN XY:

33956

show subpopulations

Gnomad4 AFR

AF:

0.0874

Gnomad4 AMR

AF:

0.0599

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.0820

Gnomad4 SAS

AF:

0.0271

Gnomad4 FIN

AF:

0.0206

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0399

Alfa

AF:

0.0237

Hom.:

362

Bravo

AF:

0.0474

EpiCase

AF:

0.0122

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.18

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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