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GeneBe

8-8797388-C-T

Variant summary

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

The NM_004225.3(MFHAS1):c.3102G>A(p.Pro1034=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,694 control chromosomes in the GnomAD database, including 28,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1882 hom., cov: 31)
Exomes 𝑓: 0.18 ( 26298 hom. )

Consequence

MFHAS1
NM_004225.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57
Variant links:
Genes affected
MFHAS1 (HGNC:16982): (multifunctional ROCO family signaling regulator 1) Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH. [provided by RefSeq, Jul 2008]

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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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-8797388-C-T is Benign according to our data. Variant chr8-8797388-C-T is described in ClinVar as [Benign]. Clinvar id is 3056038.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-1.57 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MFHAS1NM_004225.3 linkuse as main transcriptc.3102G>A p.Pro1034= synonymous_variant 2/3 ENST00000276282.7
MFHAS1XM_047422419.1 linkuse as main transcriptc.3102G>A p.Pro1034= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MFHAS1ENST00000276282.7 linkuse as main transcriptc.3102G>A p.Pro1034= synonymous_variant 2/31 NM_004225.3 P1
MFHAS1ENST00000520091.1 linkuse as main transcriptn.420G>A non_coding_transcript_exon_variant 2/44
MFHAS1ENST00000520715.5 linkuse as main transcriptn.149G>A non_coding_transcript_exon_variant 2/33
MFHAS1ENST00000521881.5 linkuse as main transcriptn.146G>A non_coding_transcript_exon_variant 2/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.140
AC:
21233
AN:
151934
Hom.:
1882
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0544
Gnomad AMI
AF:
0.191
Gnomad AMR
AF:
0.0997
Gnomad ASJ
AF:
0.173
Gnomad EAS
AF:
0.0644
Gnomad SAS
AF:
0.109
Gnomad FIN
AF:
0.192
Gnomad MID
AF:
0.124
Gnomad NFE
AF:
0.198
Gnomad OTH
AF:
0.151
GnomAD3 exomes
AF:
0.149
AC:
37557
AN:
251342
Hom.:
3229
AF XY:
0.153
AC XY:
20798
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0525
Gnomad AMR exome
AF:
0.0750
Gnomad ASJ exome
AF:
0.161
Gnomad EAS exome
AF:
0.0561
Gnomad SAS exome
AF:
0.114
Gnomad FIN exome
AF:
0.203
Gnomad NFE exome
AF:
0.199
Gnomad OTH exome
AF:
0.164
GnomAD4 exome
AF:
0.185
AC:
269789
AN:
1461642
Hom.:
26298
Cov.:
31
AF XY:
0.183
AC XY:
133204
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.0485
Gnomad4 AMR exome
AF:
0.0779
Gnomad4 ASJ exome
AF:
0.161
Gnomad4 EAS exome
AF:
0.0893
Gnomad4 SAS exome
AF:
0.114
Gnomad4 FIN exome
AF:
0.207
Gnomad4 NFE exome
AF:
0.202
Gnomad4 OTH exome
AF:
0.169
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.140
AC:
21249
AN:
152052
Hom.:
1882
Cov.:
31
AF XY:
0.138
AC XY:
10244
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0547
Gnomad4 AMR
AF:
0.0995
Gnomad4 ASJ
AF:
0.173
Gnomad4 EAS
AF:
0.0643
Gnomad4 SAS
AF:
0.110
Gnomad4 FIN
AF:
0.192
Gnomad4 NFE
AF:
0.198
Gnomad4 OTH
AF:
0.149
Alfa
AF:
0.176
Hom.:
1402
Bravo
AF:
0.127
Asia WGS
AF:
0.0900
AC:
313
AN:
3478
EpiCase
AF:
0.186
EpiControl
AF:
0.177

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MFHAS1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 20, 2019This 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
-0.53
Cadd
Benign
6.8
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs3827812; hg19: chr8-8654898; COSMIC: COSV52280706; API