chr8-8859497-T-C

Position:

• chr8-8859497-T-C

Variant summary

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

The NM_004225.3(MFHAS1):​c.2998+30564A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,174 control chromosomes in the GnomAD database, including 2,783 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 0.17 (2783 hom., cov: 32)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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]

MFHAS1 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2998+30564A>G		intron_variant		ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2998+30564A>G		intron_variant			XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+30564A>G		intron_variant		1	NM_004225.3	ENSP00000276282.6
MFHAS1	ENST00000521881.5	n.42+493A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26255 AN: 152056 Hom.: 2779 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.173 AC: 26285 AN: 152174 Hom.: 2783 Cov.: 32 AF XY: 0.171 AC XY: 12698 AN XY: 74414

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.159

Alfa AF: 0.132 Hom.: 2305

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.41

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: rs332034; hg19: chr8-8717007;