rs437895

Variant names:

• chr8-8853291-G-A
• rs437895
• NM_004225.3:c.2998+36770C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-8853291-G-A
• chr8-8853291-G-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.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
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	NM_004225.3	MANE Select	c.2998+36770C>T		intron	N/A	NP_004216.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFHAS1	ENST00000276282.7	TSL:1 MANE Select	c.2998+36770C>T		intron	N/A	ENSP00000276282.6
	MFHAS1	ENST00000521881.5	TSL:3	n.42+6699C>T		intron	N/A

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

African (AFR) AF: 0.809 AC: 33406 AN: 41300

American (AMR) AF: 0.751 AC: 11440 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2008 AN: 3470

East Asian (EAS) AF: 0.848 AC: 4368 AN: 5152

South Asian (SAS) AF: 0.756 AC: 3627 AN: 4800

European-Finnish (FIN) AF: 0.680 AC: 7115 AN: 10470

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41797 AN: 67898

Other (OTH) AF: 0.674 AC: 1415 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.44
PhyloP100		0.92
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: rs437895; hg19: chr8-8710801;