8-8783635-C-T

Variant names:

• chr8-8783635-C-T
• rs2428
• NM_004225.3:c.*2387G>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.*2387G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,914 control chromosomes in the GnomAD database, including 19,567 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 0.50 (19567 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MFHAS1 NM_004225.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 28 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.*2387G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000276282.7	NP_004216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFHAS1	ENST00000276282.7	c.*2387G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_004225.3	ENSP00000276282.6

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75222 AN: 151796 Hom.: 19540 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.495

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.496 AC: 75299 AN: 151914 Hom.: 19567 Cov.: 32 AF XY: 0.509 AC XY: 37782 AN XY: 74248

African (AFR) AF: 0.391 AC: 16183 AN: 41374

American (AMR) AF: 0.638 AC: 9739 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4408 AN: 5178

South Asian (SAS) AF: 0.674 AC: 3249 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5945 AN: 10544

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32633 AN: 67946

Other (OTH) AF: 0.500 AC: 1054 AN: 2108

Alfa AF: 0.487 Hom.: 31426

Bravo AF: 0.501

Asia WGS AF: 0.740 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		1.6
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: rs2428; hg19: chr8-8641145;