rs9822116

Positions:

• chr3-179356827-G-T

Variant summary

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

The ENST00000471841.6(MFN1):​c.249-2013G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,830 control chromosomes in the GnomAD database, including 21,957 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 (21957 hom., cov: 31)
• Consequence: MFN1 ENST00000471841.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN1	NM_033540.3	c.249-2013G>T		intron_variant		ENST00000471841.6	NP_284941.2
MFN1	XM_005247596.5	c.249-2013G>T		intron_variant			XP_005247653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN1	ENST00000471841.6	c.249-2013G>T		intron_variant		1	NM_033540.3	ENSP00000420617	P1
MFN1	ENST00000263969.9	c.249-2013G>T		intron_variant		1		ENSP00000263969	P1
MFN1	ENST00000467174.6	c.249-2013G>T		intron_variant		4		ENSP00000419134
MFN1	ENST00000357390.8	c.249-2013G>T		intron_variant, NMD_transcript_variant		2		ENSP00000349963

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78767 AN: 151712 Hom.: 21921 Cov.: 31

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.519 AC: 78847 AN: 151830 Hom.: 21957 Cov.: 31 AF XY: 0.525 AC XY: 38939 AN XY: 74190

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.484

Alfa AF: 0.445 Hom.: 26812

Bravo AF: 0.529

Asia WGS AF: 0.445 AC: 1546 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	0.78
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs9822116; hg19: chr3-179074615;