8-8828344-A-G

Variant names:

• chr8-8828344-A-G
• rs1039916
• NM_004225.3:c.2999-30853T>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.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
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	NM_004225.3	MANE Select	c.2999-30853T>C		intron	N/A	NP_004216.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	ENST00000276282.7	TSL:1 MANE Select	c.2999-30853T>C		intron	N/A	ENSP00000276282.6
	MFHAS1	ENST00000521881.5	TSL:3	n.43-30853T>C		intron	N/A

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

African (AFR) AF: 0.424 AC: 17584 AN: 41474

American (AMR) AF: 0.638 AC: 9745 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1452 AN: 3470

East Asian (EAS) AF: 0.853 AC: 4421 AN: 5184

South Asian (SAS) AF: 0.702 AC: 3387 AN: 4828

European-Finnish (FIN) AF: 0.547 AC: 5778 AN: 10558

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32921 AN: 67978

Other (OTH) AF: 0.508 AC: 1071 AN: 2108

Alfa AF: 0.473 Hom.: 8738

Bravo AF: 0.511

Asia WGS AF: 0.751 AC: 2609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.48
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1039916; hg19: chr8-8685854;