8-8869294-G-T

Variant names:

• chr8-8869294-G-T
• rs1567398
• NM_004225.3:c.2998+20767C>A

Variant summary

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

The NM_004225.3(MFHAS1):​c.2998+20767C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,970 control chromosomes in the GnomAD database, including 22,455 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 0.53 (22455 hom., cov: 32)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2998+20767C>A		intron_variant	Intron 1 of 2	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2998+20767C>A		intron_variant	Intron 1 of 2		XP_047278375.1
MFHAS1	XM_011543852.4	c.2999-2454C>A		intron_variant	Intron 1 of 1		XP_011542154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2998+20767C>A		intron_variant	Intron 1 of 2	1	NM_004225.3	ENSP00000276282.6

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80414 AN: 151852 Hom.: 22413 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.530 AC: 80516 AN: 151970 Hom.: 22455 Cov.: 32 AF XY: 0.540 AC XY: 40094 AN XY: 74296

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.513

Alfa AF: 0.471 Hom.: 4344

Bravo AF: 0.546

Asia WGS AF: 0.738 AC: 2564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.75

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: rs1567398; hg19: chr8-8726804;