7-7606175-A-G

Position:

• chr7-7606175-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MIOS	NM_019005.4	c.2531+104A>G		intron_variant		ENST00000340080.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIOS	ENST00000340080.9	c.2531+104A>G		intron_variant		1	NM_019005.4	P1
MIOS	ENST00000493227.1	n.1302+104A>G		intron_variant, non_coding_transcript_variant		1
MIOS	ENST00000405785.5	c.2531+104A>G		intron_variant		5		P1
MIOS	ENST00000479694.1	n.954+104A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.793

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.628

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.678

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.678

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

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.638

Alfa AF: 0.687 Hom.: 32433

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

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: rs2286209; hg19: chr7-7645806;