8-8889735-A-G

Position:

• chr8-8889735-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.2998+326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,164 control chromosomes in the GnomAD database, including 3,319 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 (3319 hom., cov: 33)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2998+326T>C		intron_variant		ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2998+326T>C		intron_variant			XP_047278375.1
MFHAS1	XM_011543852.4	c.2998+326T>C		intron_variant			XP_011542154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+326T>C		intron_variant		1	NM_004225.3	ENSP00000276282.6

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28252 AN: 152046 Hom.: 3302 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.186 AC: 28301 AN: 152164 Hom.: 3319 Cov.: 33 AF XY: 0.180 AC XY: 13409 AN XY: 74382

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.186

Alfa AF: 0.150 Hom.: 2606

Bravo AF: 0.196

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.42

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: rs4841067; hg19: chr8-8747245;