8-8794369-C-T

Variant names:

• chr8-8794369-C-T
• rs11774860
• NM_004225.3:c.3125+2996G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004225.3(MFHAS1):​c.3125+2996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,008 control chromosomes in the GnomAD database, including 2,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2952 hom., cov: 31)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.3125+2996G>A		intron	N/A	NP_004216.2	Q9Y4C4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	ENST00000276282.7	TSL:1 MANE Select	c.3125+2996G>A		intron	N/A	ENSP00000276282.6	Q9Y4C4
	MFHAS1	ENST00000520091.1	TSL:4	n.443+2996G>A		intron	N/A
	MFHAS1	ENST00000520715.5	TSL:3	n.172+2996G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28855 AN: 151890 Hom.: 2945 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28904 AN: 152008 Hom.: 2952 Cov.: 31 AF XY: 0.188 AC XY: 13933 AN XY: 74308

African (AFR) AF: 0.230 AC: 9525 AN: 41432

American (AMR) AF: 0.116 AC: 1771 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3468

East Asian (EAS) AF: 0.0613 AC: 317 AN: 5174

South Asian (SAS) AF: 0.106 AC: 512 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2031 AN: 10556

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13495 AN: 67968

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.181 Hom.: 4174

Bravo AF: 0.184

Asia WGS AF: 0.0970 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11774860; hg19: chr8-8651879; COSMIC: COSV52287235;