8-8794369-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.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

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 = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFHAS1	NM_004225.3	c.3125+2996G>A		intron_variant		ENST00000276282.7
MFHAS1	XM_047422419.1	c.3125+2996G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFHAS1	ENST00000276282.7	c.3125+2996G>A		intron_variant		1	NM_004225.3	P1
MFHAS1	ENST00000520091.1	n.443+2996G>A		intron_variant, non_coding_transcript_variant		4
MFHAS1	ENST00000520715.5	n.172+2996G>A		intron_variant, non_coding_transcript_variant		3
MFHAS1	ENST00000521881.5	n.169+2996G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0613

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.187

Alfa AF: 0.179 Hom.: 3420

Bravo AF: 0.184

Asia WGS AF: 0.0970 AC: 340 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	1.3
Dann	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11774860; hg19: chr8-8651879; COSMIC: COSV52287235;