8-8797388-C-T

Variant names:

• chr8-8797388-C-T
• rs3827812
• NM_004225.3:c.3102G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.57
• Publications: 11 publications found

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]

ACMG classification

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 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 rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.3102G>A	p.Pro1034Pro	synonymous_variant	Exon 2 of 3	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.3102G>A	p.Pro1034Pro	synonymous_variant	Exon 2 of 3		XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.3102G>A	p.Pro1034Pro	synonymous_variant	Exon 2 of 3	1	NM_004225.3	ENSP00000276282.6
MFHAS1	ENST00000520091.1	n.420G>A		non_coding_transcript_exon_variant	Exon 2 of 4	4
MFHAS1	ENST00000520715.5	n.149G>A		non_coding_transcript_exon_variant	Exon 2 of 3	3
MFHAS1	ENST00000521881.5	n.146G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21233 AN: 151934 Hom.: 1882 Cov.: 31

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

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.: 31 AF XY: 0.183 AC XY: 133204 AN XY: 727134

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

GnomAD4 genome AF: 0.140 AC: 21249 AN: 152052 Hom.: 1882 Cov.: 31 AF XY: 0.138 AC XY: 10244 AN XY: 74328

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: 37 AN: 292

European-Non Finnish (NFE) AF: 0.198 AC: 13438 AN: 67958

Other (OTH) AF: 0.149 AC: 314 AN: 2110

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MFHAS1-related disorder Benign:1

Nov 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3827812; hg19: chr8-8654898; COSMIC: COSV52280706;