rs4147707

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-206159383-G-C
• chr2-206159383-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFS1	NM_005006.7	c.-47C>G		5_prime_UTR_variant	Exon 1 of 19	ENST00000233190.11	NP_004997.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS1	ENST00000233190.11	c.-47C>G		5_prime_UTR_variant	Exon 1 of 19	1	NM_005006.7	ENSP00000233190.5

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

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.497

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.422

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

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.449

Alfa AF: 0.418 Hom.: 1874

Bravo AF: 0.439

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Leigh syndrome Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Mitochondrial complex I deficiency, nuclear type 1 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.9
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs4147707; hg19: chr2-207024107;