4-56972417-G-T

Variant names:

• chr4-56972417-G-T
• rs17087335
• NM_032313.4:c.1515+731C>A

Variant summary

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

The NM_032313.4(NOA1):​c.1515+731C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,094 control chromosomes in the GnomAD database, including 3,353 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 0.21 (3353 hom., cov: 32)
• Consequence: NOA1 NM_032313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 52 publications found

Genes affected

NOA1 (HGNC:28473): (nitric oxide associated 1) The protein encoded by this gene is a nuclear-encoded GTPase that functions in the mitochondrion. Upon translation, this protein is imported into the nucleus and then into the nucleolus before being exported to the mitochondrion. The encoded protein is required for oxygen-dependent regulation of mitochondrial respiratory complexes and for mitochondrial protein synthesis. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOA1	NM_032313.4	c.1515+731C>A		intron_variant	Intron 3 of 6	ENST00000264230.5	NP_115689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOA1	ENST00000264230.5	c.1515+731C>A		intron_variant	Intron 3 of 6	1	NM_032313.4	ENSP00000264230.4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31344 AN: 151976 Hom.: 3346 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.206 AC: 31374 AN: 152094 Hom.: 3353 Cov.: 32 AF XY: 0.209 AC XY: 15524 AN XY: 74368

African (AFR) AF: 0.196 AC: 8115 AN: 41490

American (AMR) AF: 0.205 AC: 3140 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2074 AN: 5156

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4824

European-Finnish (FIN) AF: 0.235 AC: 2494 AN: 10592

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13156 AN: 67976

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.196 Hom.: 8328

Bravo AF: 0.203

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs17087335; hg19: chr4-57838583;