2-37240121-T-C

Variant names:

• chr2-37240121-T-C
• rs2041840
• NM_144736.5:c.409-1457T>C

Variant summary

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

The NM_144736.5(NDUFAF7):​c.409-1457T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,064 control chromosomes in the GnomAD database, including 40,421 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 0.72 (40421 hom., cov: 33)
• Consequence: NDUFAF7 NM_144736.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 18 publications found

Genes affected

NDUFAF7 (HGNC:28816): (NADH:ubiquinone oxidoreductase complex assembly factor 7) This gene encodes an assembly factor protein which helps in the assembly and stabilization of Complex I, a large multi-subunit enzyme in the mitochondrial respiratory chain. Complex I is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. The encoded protein is a methyltransferase which methylates Arg85 of a subunit of Complex I in the early stages of its assembly. A pseudogene related to this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144736.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF7	NM_144736.5	MANE Select	c.409-1457T>C		intron	N/A	NP_653337.1	Q7L592-1
	NDUFAF7	NM_001350024.2		c.409-1457T>C		intron	N/A	NP_001336953.1
	NDUFAF7	NM_001350025.2		c.328-1457T>C		intron	N/A	NP_001336954.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF7	ENST00000002125.9	TSL:1 MANE Select	c.409-1457T>C		intron	N/A	ENSP00000002125.4	Q7L592-1
	NDUFAF7	ENST00000336237.10	TSL:1	c.328-1457T>C		intron	N/A	ENSP00000337431.6	Q7L592-2
	NDUFAF7	ENST00000885393.1		c.409-1457T>C		intron	N/A	ENSP00000555452.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109607 AN: 151948 Hom.: 40386 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.721 AC: 109695 AN: 152064 Hom.: 40421 Cov.: 33 AF XY: 0.726 AC XY: 53973 AN XY: 74342

African (AFR) AF: 0.821 AC: 34062 AN: 41480

American (AMR) AF: 0.809 AC: 12365 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5087 AN: 5184

South Asian (SAS) AF: 0.680 AC: 3276 AN: 4816

European-Finnish (FIN) AF: 0.697 AC: 7369 AN: 10576

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42674 AN: 67948

Other (OTH) AF: 0.748 AC: 1578 AN: 2110

Alfa AF: 0.660 Hom.: 95084

Bravo AF: 0.739

Asia WGS AF: 0.857 AC: 2979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.38
PhyloP100		-0.59
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: rs2041840; hg19: chr2-37467264;