2-201078708-A-G

Variant names:

• chr2-201078708-A-G
• rs11887751
• NM_002491.3:c.-2-173A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002491.3(NDUFB3):​c.-2-173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,080 control chromosomes in the GnomAD database, including 472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.052 (472 hom., cov: 32)
• Consequence: NDUFB3 NM_002491.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.401

Genes affected

NDUFB3 (HGNC:7698): (NADH:ubiquinone oxidoreductase subunit B3) This gene encodes an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which is the first enzyme in the electron transport chain of mitochondria. This protein localizes to the inner membrane of the mitochondrion as a single-pass membrane protein. Mutations in this gene contribute to mitochondrial complex 1 deficiency. Alternative splicing results in multiple transcript variants encoding the same protein. Humans have multiple pseudogenes of this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-201078708-A-G is Benign according to our data. Variant chr2-201078708-A-G is described in ClinVar as [Benign]. Clinvar id is 675479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB3	NM_002491.3	c.-2-173A>G		intron_variant	Intron 1 of 2	ENST00000237889.9	NP_002482.1
NDUFB3	NM_001257102.2	c.-2-173A>G		intron_variant	Intron 2 of 3		NP_001244031.1
NDUFB3	XM_011511230.4	c.-2-173A>G		intron_variant	Intron 2 of 3		XP_011509532.1
NDUFB3	XM_047444488.1	c.-2-173A>G		intron_variant	Intron 2 of 3		XP_047300444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB3	ENST00000237889.9	c.-2-173A>G		intron_variant	Intron 1 of 2	1	NM_002491.3	ENSP00000237889.4

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7876 AN: 151968 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0158

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0519 AC: 7890 AN: 152080 Hom.: 472 Cov.: 32 AF XY: 0.0514 AC XY: 3825 AN XY: 74354

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0158

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0221 Hom.: 74

Bravo AF: 0.0560

Asia WGS AF: 0.0140 AC: 50 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.57

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: rs11887751; hg19: chr2-201943431;