Variant chr8-8797388-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004225.3(MFHAS1):c.3102G>A(p.Pro1034Pro) 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 (no stars).

Frequency

Genomes: 𝑓 0.14 ( 1882 hom., cov: 31)

Exomes 𝑓: 0.18 ( 26298 hom. )

Consequence

MFHAS1
NM_004225.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided 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]

MFHAS1 links:

MFHAS1 (HGNC:):

MFHAS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

BA1

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	Protein	UniProt
MFHAS1	NM_004225.3 linkuse as main transcript	c.3102G>A	p.Pro1034Pro	synonymous_variant	2/3	ENST00000276282.7	NP_004216.2	Q9Y4C4
MFHAS1	XM_047422419.1 linkuse as main transcript	c.3102G>A	p.Pro1034Pro	synonymous_variant	2/3		XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFHAS1	ENST00000276282.7 linkuse as main transcript	c.3102G>A	p.Pro1034Pro	synonymous_variant	2/3	1	NM_004225.3	ENSP00000276282.6	Q9Y4C4
MFHAS1	ENST00000520091.1 linkuse as main transcript	n.420G>A		non_coding_transcript_exon_variant	2/4	4
MFHAS1	ENST00000520715.5 linkuse as main transcript	n.149G>A		non_coding_transcript_exon_variant	2/3	3
MFHAS1	ENST00000521881.5 linkuse as main transcript	n.146G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21233

AN:

151934

Hom.:

1882

Cov.:

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.:

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

AF:

0.140

AC:

21249

AN:

152052

Hom.:

1882

Cov.:

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: no assertion criteria provided

LINK: link

Submissions by phenotype

MFHAS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This 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.

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