NM_005006.7:c.-47C>G

Variant names:

• chr2-206159383-G-C
• rs4147707
• NM_005006.7:c.-47C>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005006.7(NDUFS1):​c.-47C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 559,318 control chromosomes in the GnomAD database, including 47,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14579 hom., cov: 33)
  • Exomes 𝑓: 0.40 (32872 hom.)
• Consequence: NDUFS1 NM_005006.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.346
• Publications: 10 publications found

Genes affected

NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

EEF1B2 (HGNC:3208): (eukaryotic translation elongation factor 1 beta 2) This gene encodes a translation elongation factor. The protein is a guanine nucleotide exchange factor involved in the transfer of aminoacylated tRNAs to the ribosome. Alternative splicing results in three transcript variants which differ only in the 5' UTR. [provided by RefSeq, Jul 2008]

EEF1B2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-206159383-G-C is Benign according to our data. Variant chr2-206159383-G-C is described in ClinVar as Benign. ClinVar VariationId is 333790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005006.7. 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
	NDUFS1	NM_005006.7	MANE Select	c.-47C>G		5_prime_UTR	Exon 1 of 19	NP_004997.4
	NDUFS1	NM_001199981.2		c.-47C>G		5_prime_UTR	Exon 1 of 18	NP_001186910.1	P28331-5
	NDUFS1	NM_001199983.2		c.-126C>G		5_prime_UTR	Exon 1 of 18	NP_001186912.1	P28331-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS1	ENST00000233190.11	TSL:1 MANE Select	c.-47C>G		5_prime_UTR	Exon 1 of 19	ENSP00000233190.5	P28331-1
	NDUFS1	ENST00000903706.1		c.-47C>G		5_prime_UTR	Exon 1 of 19	ENSP00000573765.1
	NDUFS1	ENST00000938122.1		c.-118C>G		5_prime_UTR	Exon 1 of 20	ENSP00000608181.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65611 AN: 151964 Hom.: 14557 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.453

GnomAD4 exome AF: 0.396 AC: 161148 AN: 407236 Hom.: 32872 Cov.: 3 AF XY: 0.390 AC XY: 83312 AN XY: 213414

African (AFR) AF: 0.509 AC: 5911 AN: 11624

American (AMR) AF: 0.483 AC: 8397 AN: 17382

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 6233 AN: 12542

East Asian (EAS) AF: 0.208 AC: 6087 AN: 29222

South Asian (SAS) AF: 0.298 AC: 11368 AN: 38170

European-Finnish (FIN) AF: 0.441 AC: 12043 AN: 27294

Middle Eastern (MID) AF: 0.509 AC: 914 AN: 1796

European-Non Finnish (NFE) AF: 0.408 AC: 100055 AN: 245192

Other (OTH) AF: 0.422 AC: 10140 AN: 24014

GnomAD4 genome AF: 0.432 AC: 65684 AN: 152082 Hom.: 14579 Cov.: 33 AF XY: 0.431 AC XY: 32017 AN XY: 74340

African (AFR) AF: 0.499 AC: 20704 AN: 41472

American (AMR) AF: 0.481 AC: 7350 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1760 AN: 3466

East Asian (EAS) AF: 0.225 AC: 1166 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4814

European-Finnish (FIN) AF: 0.447 AC: 4729 AN: 10576

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27308 AN: 67988

Other (OTH) AF: 0.449 AC: 950 AN: 2116

Alfa AF: 0.418 Hom.: 1874

Bravo AF: 0.439

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Leigh syndrome (1)
-	-	1	Mitochondrial complex I deficiency, nuclear type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.9
DANN	Benign	0.60
PhyloP100		0.35
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	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: rs4147707; hg19: chr2-207024107;