rs4121165

Positions:

• chr1-77811292-G-A

Variant summary

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

The ENST00000370791.9(MIGA1):​c.542-2442G>A variant causes a intron change. The variant allele was found at a frequency of 0.204 in 1,596,166 control chromosomes in the GnomAD database, including 35,507 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 0.20 (3105 hom., cov: 30)
  • Exomes 𝑓: 0.20 (32402 hom.)
• Consequence: MIGA1 ENST00000370791.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99

Genes affected

MIGA1 (HGNC:24741): (mitoguardin 1) Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Located in mitochondrion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIGA1	NM_001416120.1	c.542-2442G>A		intron_variant		ENST00000370791.9	NP_001403049.1
MIGA1	NM_001270384.2	c.638-2442G>A		intron_variant			NP_001257313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIGA1	ENST00000370791.9	c.542-2442G>A		intron_variant		1	NM_001416120.1	ENSP00000359827	P4
	ENST00000427577.1	n.490C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29734 AN: 151872 Hom.: 3107 Cov.: 30

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.205 AC: 295783 AN: 1444174 Hom.: 32402 Cov.: 33 AF XY: 0.201 AC XY: 144593 AN XY: 719300

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.0766

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.196 AC: 29735 AN: 151992 Hom.: 3105 Cov.: 30 AF XY: 0.191 AC XY: 14210 AN XY: 74286

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.0753

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.186

Alfa AF: 0.206 Hom.: 3025

Bravo AF: 0.202

Asia WGS AF: 0.216 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.4
DANN	Benign	0.84

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: rs4121165; hg19: chr1-78276977; COSMIC: COSV66223763;