rs4121165

Variant names:

• chr1-77811292-G-A
• rs4121165
• NM_198549.4:c.638-2442G>A

Variant summary

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

The NM_198549.4(MIGA1):​c.638-2442G>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 NM_198549.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99
• Publications: 10 publications found

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]

ENSG00000219201 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MIGA1	NM_198549.4	c.638-2442G>A		intron_variant	Intron 5 of 15	ENST00000370791.8	NP_940951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIGA1	ENST00000370791.9	c.542-2442G>A		intron_variant	Intron 5 of 15	1		ENSP00000359827.4

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

African (AFR) AF: 0.183 AC: 6043 AN: 33104

American (AMR) AF: 0.167 AC: 7462 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5603 AN: 26018

East Asian (EAS) AF: 0.423 AC: 16746 AN: 39620

South Asian (SAS) AF: 0.0766 AC: 6585 AN: 85954

European-Finnish (FIN) AF: 0.166 AC: 8884 AN: 53388

Middle Eastern (MID) AF: 0.176 AC: 939 AN: 5348

European-Non Finnish (NFE) AF: 0.211 AC: 231031 AN: 1096290

Other (OTH) AF: 0.209 AC: 12490 AN: 59760

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

African (AFR) AF: 0.173 AC: 7186 AN: 41438

American (AMR) AF: 0.170 AC: 2588 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 741 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2249 AN: 5150

South Asian (SAS) AF: 0.0753 AC: 362 AN: 4810

European-Finnish (FIN) AF: 0.159 AC: 1680 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14253 AN: 67970

Other (OTH) AF: 0.186 AC: 391 AN: 2106

Alfa AF: 0.203 Hom.: 3944

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
PhyloP100		7.0
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: rs4121165; hg19: chr1-78276977; COSMIC: COSV66223763;