rs2111534

Positions:

• chr3-179372984-G-A

Variant summary

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

The NM_033540.3(MFN1):​c.976-2236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,826 control chromosomes in the GnomAD database, including 22,016 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 0.52 (22016 hom., cov: 31)
• Consequence: MFN1 NM_033540.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

MFN1 (HGNC:18262): (mitofusin 1) The protein encoded by this gene is a mediator of mitochondrial fusion. This protein and mitofusin 2 are homologs of the Drosophila protein fuzzy onion (Fzo). They are mitochondrial membrane proteins that interact with each other to facilitate mitochondrial targeting. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN1	NM_033540.3	c.976-2236G>A		intron_variant		ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.976-2236G>A		intron_variant			XP_005247653.2
MFN1	XM_011512963.4	c.535-2236G>A		intron_variant			XP_011511265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.976-2236G>A		intron_variant		1	NM_033540.3	ENSP00000420617.1
MFN1	ENST00000263969.9	c.976-2236G>A		intron_variant		1		ENSP00000263969.5
MFN1	ENST00000474903.1	c.565-2236G>A		intron_variant		1		ENSP00000419926.1
MFN1	ENST00000357390.8	n.976-2236G>A		intron_variant		2		ENSP00000349963.4

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78870 AN: 151710 Hom.: 21980 Cov.: 31

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.520 AC: 78949 AN: 151826 Hom.: 22016 Cov.: 31 AF XY: 0.526 AC XY: 39001 AN XY: 74192

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.485

Alfa AF: 0.451 Hom.: 16597

Bravo AF: 0.529

Asia WGS AF: 0.442 AC: 1535 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2111534; hg19: chr3-179090772;