chr8-8889735-A-G

Variant names:

• chr8-8889735-A-G
• rs4841067
• NM_004225.3:c.2998+326T>C

Variant summary

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

The NM_004225.3(MFHAS1):​c.2998+326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,164 control chromosomes in the GnomAD database, including 3,319 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 (3319 hom., cov: 33)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 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.2998+326T>C		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.2998+326T>C		intron	N/A	ENSP00000276282.6	Q9Y4C4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28252 AN: 152046 Hom.: 3302 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.186 AC: 28301 AN: 152164 Hom.: 3319 Cov.: 33 AF XY: 0.180 AC XY: 13409 AN XY: 74382

African (AFR) AF: 0.326 AC: 13506 AN: 41478

American (AMR) AF: 0.127 AC: 1937 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.133 AC: 642 AN: 4826

European-Finnish (FIN) AF: 0.0841 AC: 892 AN: 10606

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.147 AC: 10013 AN: 67994

Other (OTH) AF: 0.186 AC: 393 AN: 2116

Alfa AF: 0.157 Hom.: 3636

Bravo AF: 0.196

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.42
PhyloP100		0.0
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: rs4841067; hg19: chr8-8747245;