chr7-7606175-A-G

Variant names:

• chr7-7606175-A-G
• rs2286209
• NM_019005.4:c.2531+104A>G

Variant summary

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

The NM_019005.4(MIOS):​c.2531+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,415,508 control chromosomes in the GnomAD database, including 336,313 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 0.63 (31195 hom., cov: 32)
  • Exomes 𝑓: 0.69 (305118 hom.)
• Consequence: MIOS NM_019005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 6 publications found

Genes affected

MIOS (HGNC:21905): (meiosis regulator for oocyte development) Involved in cellular response to amino acid starvation; positive regulation of TOR signaling; and protein-containing complex localization. Located in several cellular components, including cytosol; lysosomal membrane; and nucleoplasm. Part of GATOR2 complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293795 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOS	NM_019005.4	c.2531+104A>G		intron_variant	Intron 12 of 12	ENST00000340080.9	NP_061878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOS	ENST00000340080.9	c.2531+104A>G		intron_variant	Intron 12 of 12	1	NM_019005.4	ENSP00000339881.4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95790 AN: 151864 Hom.: 31181 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.692 AC: 874638 AN: 1263526 Hom.: 305118 AF XY: 0.693 AC XY: 431833 AN XY: 623504

African (AFR) AF: 0.435 AC: 12330 AN: 28334

American (AMR) AF: 0.793 AC: 24096 AN: 30380

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 13043 AN: 20062

East Asian (EAS) AF: 0.628 AC: 23629 AN: 37654

South Asian (SAS) AF: 0.672 AC: 42335 AN: 62968

European-Finnish (FIN) AF: 0.678 AC: 31823 AN: 46970

Middle Eastern (MID) AF: 0.615 AC: 3140 AN: 5104

European-Non Finnish (NFE) AF: 0.703 AC: 688630 AN: 979564

Other (OTH) AF: 0.678 AC: 35612 AN: 52490

GnomAD4 genome AF: 0.631 AC: 95830 AN: 151982 Hom.: 31195 Cov.: 32 AF XY: 0.632 AC XY: 46962 AN XY: 74318

African (AFR) AF: 0.453 AC: 18759 AN: 41426

American (AMR) AF: 0.752 AC: 11477 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3426 AN: 5158

South Asian (SAS) AF: 0.669 AC: 3231 AN: 4828

European-Finnish (FIN) AF: 0.672 AC: 7101 AN: 10562

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47380 AN: 67966

Other (OTH) AF: 0.638 AC: 1343 AN: 2104

Alfa AF: 0.684 Hom.: 38956

Bravo AF: 0.633

Asia WGS AF: 0.607 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		0.16
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: rs2286209; hg19: chr7-7645806;