8-8801528-C-T

Variant names:

• chr8-8801528-C-T
• rs3827811
• NM_004225.3:c.2999-4037G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004225.3(MFHAS1):​c.2999-4037G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,042 control chromosomes in the GnomAD database, including 7,958 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 0.31 (7958 hom., cov: 32)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95
• Publications: 8 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2999-4037G>A		intron_variant	Intron 1 of 2	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2999-4037G>A		intron_variant	Intron 1 of 2		XP_047278375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.2999-4037G>A		intron_variant	Intron 1 of 2	1	NM_004225.3	ENSP00000276282.6
MFHAS1	ENST00000520091.1	n.317-4037G>A		intron_variant	Intron 1 of 3	4
MFHAS1	ENST00000520715.5	n.46-4037G>A		intron_variant	Intron 1 of 2	3
MFHAS1	ENST00000521881.5	n.43-4037G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47520 AN: 151924 Hom.: 7940 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.313 AC: 47567 AN: 152042 Hom.: 7958 Cov.: 32 AF XY: 0.310 AC XY: 23064 AN XY: 74320

African (AFR) AF: 0.412 AC: 17110 AN: 41500

American (AMR) AF: 0.197 AC: 3010 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3466

East Asian (EAS) AF: 0.119 AC: 617 AN: 5178

South Asian (SAS) AF: 0.352 AC: 1694 AN: 4816

European-Finnish (FIN) AF: 0.270 AC: 2850 AN: 10562

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20316 AN: 67926

Other (OTH) AF: 0.300 AC: 633 AN: 2110

Alfa AF: 0.287 Hom.: 10856

Bravo AF: 0.305

Asia WGS AF: 0.234 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.65
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3827811; hg19: chr8-8659038;