rs10108954

Positions:

• chr8-8864868-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MFHAS1	NM_004225.3	c.2998+25193G>A		intron_variant		ENST00000276282.7
MFHAS1	XM_047422419.1	c.2998+25193G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+25193G>A		intron_variant		1	NM_004225.3	P1

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

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.00794

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0439 Hom.: 944

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10108954; hg19: chr8-8722378;