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rs2235708

chrX-139596585-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chrX-139596585-G-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.153 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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
MCF2NM_001171876.2 linkuse as main transcriptc.2469C>T p.Asp823= synonymous_variant 23/29 ENST00000519895.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCF2ENST00000519895.6 linkuse as main transcriptc.2469C>T p.Asp823= synonymous_variant 23/292 NM_001171876.2 P4P10911-5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0408
AC:
4555
AN:
111641
Hom.:
116
Cov.:
23
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0408
AC:
4559
AN:
111694
Hom.:
116
Cov.:
23
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:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 13, 2019- -

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.

Other links and lift over

dbSNP: rs2235708; hg19: chrX-138678744; COSMIC: COSV58491739; API