8-8828344-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004225.3(MFHAS1):c.2999-30853T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,076 control chromosomes in the GnomAD database, including 20,278 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 0.51 (20278 hom., cov: 33)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFHAS1	NM_004225.3	c.2999-30853T>C		intron_variant		ENST00000276282.7
MFHAS1	XM_047422419.1	c.2999-30853T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2999-30853T>C		intron_variant		1	NM_004225.3	P1
MFHAS1	ENST00000521881.5	n.43-30853T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76920 AN: 151958 Hom.: 20258 Cov.: 33

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.506 AC: 76988 AN: 152076 Hom.: 20278 Cov.: 33 AF XY: 0.518 AC XY: 38458 AN XY: 74314

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.508

Alfa AF: 0.473 Hom.: 7818

Bravo AF: 0.511

Asia WGS AF: 0.751 AC: 2609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.36
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1039916; hg19: chr8-8685854;