rs2288414

Variant names:

• chr19-8320768-C-G
• rs2288414
• NM_005001.5:c.101+89G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-8320768-C-G
• chr19-8320768-C-T

Variant summary

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

The NM_005001.5(NDUFA7):​c.101+89G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,502,462 control chromosomes in the GnomAD database, including 6,006 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 0.13 (2798 hom., cov: 32)
  • Exomes 𝑓: 0.045 (3208 hom.)
• Consequence: NDUFA7 NM_005001.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 6 publications found

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

ENSG00000167774 (HGNC:):

RPS28 (HGNC:10418): (ribosomal protein S28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S28E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPS28 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005001.5. 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
	NDUFA7	NM_005001.5	MANE Select	c.101+89G>C		intron	N/A	NP_004992.2	O95182
	NDUFA7	NR_135539.2		n.118+89G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFA7	ENST00000301457.3	TSL:1 MANE Select	c.101+89G>C		intron	N/A	ENSP00000301457.1	O95182
	ENSG00000167774	ENST00000598884.1	TSL:4	n.101+89G>C		intron	N/A	ENSP00000470609.1
	NDUFA7	ENST00000930188.1		c.101+89G>C		intron	N/A	ENSP00000600247.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19760 AN: 152042 Hom.: 2780 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0888

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0449 AC: 60688 AN: 1350302 Hom.: 3208 AF XY: 0.0436 AC XY: 29429 AN XY: 674820

African (AFR) AF: 0.368 AC: 11364 AN: 30888

American (AMR) AF: 0.0501 AC: 2186 AN: 43638

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 1493 AN: 24660

East Asian (EAS) AF: 0.0728 AC: 2825 AN: 38812

South Asian (SAS) AF: 0.0346 AC: 2859 AN: 82730

European-Finnish (FIN) AF: 0.0282 AC: 1468 AN: 52058

Middle Eastern (MID) AF: 0.0672 AC: 370 AN: 5510

European-Non Finnish (NFE) AF: 0.0341 AC: 34628 AN: 1015570

Other (OTH) AF: 0.0619 AC: 3495 AN: 56436

GnomAD4 genome AF: 0.130 AC: 19816 AN: 152160 Hom.: 2798 Cov.: 32 AF XY: 0.129 AC XY: 9597 AN XY: 74388

African (AFR) AF: 0.360 AC: 14915 AN: 41478

American (AMR) AF: 0.0716 AC: 1093 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.0890 AC: 461 AN: 5178

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4828

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0348 AC: 2369 AN: 68016

Other (OTH) AF: 0.110 AC: 232 AN: 2106

Alfa AF: 0.0850 Hom.: 185

Bravo AF: 0.144

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		-0.45
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: rs2288414; hg19: chr19-8385652;