Genetic Variant NM_004225.3:c.3102G>A (chr8-8797388-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	NM_004225.3	MANE Select	c.3102G>A	p.Pro1034Pro	synonymous	Exon 2 of 3	NP_004216.2	Q9Y4C4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFHAS1	ENST00000276282.7	TSL:1 MANE Select	c.3102G>A	p.Pro1034Pro	synonymous	Exon 2 of 3	ENSP00000276282.6	Q9Y4C4
MFHAS1	ENST00000520091.1	TSL:4	n.420G>A		non_coding_transcript_exon	Exon 2 of 4
MFHAS1	ENST00000520715.5	TSL:3	n.149G>A		non_coding_transcript_exon	Exon 2 of 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

GnomAD2 exomes

AF:

0.149

AC:

37557

AN:

251342

AF XY:

0.153

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 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

African (AFR)

AF:

0.0485

AC:

1622

AN:

33474

American (AMR)

AF:

0.0779

AC:

3482

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4202

AN:

26136

East Asian (EAS)

AF:

0.0893

AC:

3546

AN:

39688

South Asian (SAS)

AF:

0.114

AC:

9859

AN:

86250

European-Finnish (FIN)

AF:

0.207

AC:

11033

AN:

53410

Middle Eastern (MID)

AF:

0.134

AC:

773

AN:

5768

European-Non Finnish (NFE)

AF:

0.202

AC:

225066

AN:

1111812

Other (OTH)

AF:

0.169

AC:

10206

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11025

22050

33076

44101

55126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7650

15300

22950

30600

38250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.140

AC:

21249

AN:

152052

Hom.:

1882

Cov.:

AF XY:

0.138

AC XY:

10244

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0547

AC:

2268

AN:

41484

American (AMR)

AF:

0.0995

AC:

1520

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

602

AN:

3472

East Asian (EAS)

AF:

0.0643

AC:

332

AN:

5162

South Asian (SAS)

AF:

0.110

AC:

529

AN:

4814

European-Finnish (FIN)

AF:

0.192

AC:

2035

AN:

10578

Middle Eastern (MID)

AF:

0.127

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.198

AC:

13438

AN:

67958

Other (OTH)

AF:

0.149

AC:

314

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

882

1764

2647

3529

4411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.177

Hom.:

1755

Bravo

AF:

0.127

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.177

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MFHAS1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.8

(source)

DANN

Benign

0.87

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over