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GeneBe

8-8890548-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_004225.3(MFHAS1):c.2511G>A(p.Lys837=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,613,534 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 10 hom. )

Consequence

MFHAS1
NM_004225.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.567
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=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-8890548-C-T is Benign according to our data. Variant chr8-8890548-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=0.567 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MFHAS1NM_004225.3 linkuse as main transcriptc.2511G>A p.Lys837= synonymous_variant 1/3 ENST00000276282.7
MFHAS1XM_047422419.1 linkuse as main transcriptc.2511G>A p.Lys837= synonymous_variant 1/3
MFHAS1XM_011543852.4 linkuse as main transcriptc.2511G>A p.Lys837= synonymous_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MFHAS1ENST00000276282.7 linkuse as main transcriptc.2511G>A p.Lys837= synonymous_variant 1/31 NM_004225.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00171
AC:
260
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000981
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00496
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00284
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00195
AC:
490
AN:
250754
Hom.:
3
AF XY:
0.00221
AC XY:
299
AN XY:
135562
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.00116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00203
Gnomad FIN exome
AF:
0.000664
Gnomad NFE exome
AF:
0.00314
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00283
AC:
4133
AN:
1461168
Hom.:
10
Cov.:
80
AF XY:
0.00288
AC XY:
2091
AN XY:
726894
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00255
Gnomad4 FIN exome
AF:
0.00106
Gnomad4 NFE exome
AF:
0.00331
Gnomad4 OTH exome
AF:
0.00187
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00169
AC:
258
AN:
152366
Hom.:
0
Cov.:
33
AF XY:
0.00164
AC XY:
122
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000481
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00455
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00284
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00203
Hom.:
0
Bravo
AF:
0.00139
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00273
EpiControl
AF:
0.00213

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

MFHAS1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 01, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023MFHAS1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
9.1
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs146502253; hg19: chr8-8748058; API