chr8-8864868-C-T

Variant names:

• chr8-8864868-C-T
• rs10108954
• NM_004225.3:c.2998+25193G>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.2998+25193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,042 control chromosomes in the GnomAD database, including 2,872 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 0.13 (2872 hom., cov: 32)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 7 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 = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2998+25193G>A		intron_variant	Intron 1 of 2	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2998+25193G>A		intron_variant	Intron 1 of 2		XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+25193G>A		intron_variant	Intron 1 of 2	1	NM_004225.3	ENSP00000276282.6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19193 AN: 151924 Hom.: 2860 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.00794

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.127 AC: 19243 AN: 152042 Hom.: 2872 Cov.: 32 AF XY: 0.124 AC XY: 9186 AN XY: 74344

African (AFR) AF: 0.363 AC: 15032 AN: 41416

American (AMR) AF: 0.0976 AC: 1490 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0676 AC: 325 AN: 4808

European-Finnish (FIN) AF: 0.00794 AC: 84 AN: 10584

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1976 AN: 67994

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0585 Hom.: 3912

Bravo AF: 0.142

Asia WGS AF: 0.0500 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.37
PhyloP100		-1.0
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: rs10108954; hg19: chr8-8722378;