chr7-7572218-G-C

Variant names:

• chr7-7572218-G-C
• rs10236767
• NM_019005.4:c.-40-218G>C

Variant summary

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

The NM_019005.4(MIOS):​c.-40-218G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,022 control chromosomes in the GnomAD database, including 37,409 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 0.70 (37409 hom., cov: 32)
• Consequence: MIOS NM_019005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 4 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOS	NM_019005.4	c.-40-218G>C		intron_variant	Intron 3 of 12	ENST00000340080.9	NP_061878.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIOS	ENST00000340080.9	c.-40-218G>C		intron_variant	Intron 3 of 12	1	NM_019005.4	ENSP00000339881.4

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106497 AN: 151904 Hom.: 37372 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.701 AC: 106577 AN: 152022 Hom.: 37409 Cov.: 32 AF XY: 0.699 AC XY: 51907 AN XY: 74286

African (AFR) AF: 0.692 AC: 28661 AN: 41436

American (AMR) AF: 0.771 AC: 11777 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2198 AN: 3472

East Asian (EAS) AF: 0.656 AC: 3387 AN: 5162

South Asian (SAS) AF: 0.632 AC: 3045 AN: 4818

European-Finnish (FIN) AF: 0.684 AC: 7225 AN: 10562

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.705 AC: 47937 AN: 67974

Other (OTH) AF: 0.682 AC: 1440 AN: 2110

Alfa AF: 0.693 Hom.: 4514

Bravo AF: 0.712

Asia WGS AF: 0.609 AC: 2120 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.75
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: rs10236767; hg19: chr7-7611849;