rs17154769

Variant names:

• chr8-8802049-A-G
• rs17154769
• NM_004225.3:c.2999-4558T>C

Variant summary

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

The NM_004225.3(MFHAS1):​c.2999-4558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,152 control chromosomes in the GnomAD database, including 6,246 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 0.22 (6246 hom., cov: 33)
• Consequence: MFHAS1 NM_004225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFHAS1	NM_004225.3	c.2999-4558T>C		intron_variant	Intron 1 of 2	ENST00000276282.7	NP_004216.2
MFHAS1	XM_047422419.1	c.2999-4558T>C		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.2999-4558T>C		intron_variant	Intron 1 of 2	1	NM_004225.3	ENSP00000276282.6
MFHAS1	ENST00000520091.1	n.317-4558T>C		intron_variant	Intron 1 of 3	4
MFHAS1	ENST00000520715.5	n.46-4558T>C		intron_variant	Intron 1 of 2	3
MFHAS1	ENST00000521881.5	n.43-4558T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33207 AN: 152034 Hom.: 6225 Cov.: 33

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.219 AC: 33262 AN: 152152 Hom.: 6246 Cov.: 33 AF XY: 0.216 AC XY: 16055 AN XY: 74404

African (AFR) AF: 0.512 AC: 21205 AN: 41442

American (AMR) AF: 0.110 AC: 1683 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 451 AN: 3472

East Asian (EAS) AF: 0.0553 AC: 287 AN: 5192

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4820

European-Finnish (FIN) AF: 0.0782 AC: 830 AN: 10614

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7152 AN: 68006

Other (OTH) AF: 0.178 AC: 376 AN: 2112

Alfa AF: 0.136 Hom.: 3847

Bravo AF: 0.229

Asia WGS AF: 0.159 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		-0.040
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: rs17154769; hg19: chr8-8659559;