rs437895

Positions:

• chr8-8853291-G-A
• chr8-8853291-G-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+36770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,634 control chromosomes in the GnomAD database, including 37,666 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 0.70 (37666 hom., cov: 29)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917

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 (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2998+36770C>T		intron_variant		ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2998+36770C>T		intron_variant			XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+36770C>T		intron_variant		1	NM_004225.3	ENSP00000276282.6
MFHAS1	ENST00000521881.5	n.42+6699C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.699 AC: 105884 AN: 151516 Hom.: 37612 Cov.: 29

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.699 AC: 106001 AN: 151634 Hom.: 37666 Cov.: 29 AF XY: 0.705 AC XY: 52257 AN XY: 74076

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.674

Alfa AF: 0.638 Hom.: 6229

Bravo AF: 0.712

Asia WGS AF: 0.785 AC: 2731 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	2.8
DANN	Benign	0.44

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: rs437895; hg19: chr8-8710801;