8-8890548-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_004225.3(MFHAS1):c.2511G>A(p.Lys837Lys) 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
NM_004225.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.567
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
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_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.567 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MFHAS1 | NM_004225.3 | c.2511G>A | p.Lys837Lys | synonymous_variant | 1/3 | ENST00000276282.7 | NP_004216.2 | |
MFHAS1 | XM_047422419.1 | c.2511G>A | p.Lys837Lys | synonymous_variant | 1/3 | XP_047278375.1 | ||
MFHAS1 | XM_011543852.4 | c.2511G>A | p.Lys837Lys | synonymous_variant | 1/2 | XP_011542154.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00171 AC: 260AN: 152248Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
260
AN:
152248
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00195 AC: 490AN: 250754Hom.: 3 AF XY: 0.00221 AC XY: 299AN XY: 135562
GnomAD3 exomes
AF:
AC:
490
AN:
250754
Hom.:
AF XY:
AC XY:
299
AN XY:
135562
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00283 AC: 4133AN: 1461168Hom.: 10 Cov.: 80 AF XY: 0.00288 AC XY: 2091AN XY: 726894
GnomAD4 exome
AF:
AC:
4133
AN:
1461168
Hom.:
Cov.:
80
AF XY:
AC XY:
2091
AN XY:
726894
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00169 AC: 258AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.00164 AC XY: 122AN XY: 74504
GnomAD4 genome
AF:
AC:
258
AN:
152366
Hom.:
Cov.:
33
AF XY:
AC XY:
122
AN XY:
74504
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MFHAS1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 01, 2019 | This 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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | MFHAS1: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at