chr19-8321422-G-A

Position:

• chr19-8321422-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000449223.3(RPS28):​n.265G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,520,650 control chromosomes in the GnomAD database, including 31,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2055 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29097 hom.)
• Consequence: RPS28 ENST00000449223.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-8321422-G-A is Benign according to our data. Variant chr19-8321422-G-A is described in ClinVar as [Benign]. Clinvar id is 1276445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA7	NM_005001.5			upstream_gene_variant		ENST00000301457.3	NP_004992.2
NDUFA7	NR_135539.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3			upstream_gene_variant		1	NM_005001.5	ENSP00000301457	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22609 AN: 152140 Hom.: 2056 Cov.: 32

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.200 AC: 273919 AN: 1368392 Hom.: 29097 Cov.: 32 AF XY: 0.198 AC XY: 132978 AN XY: 669980

Gnomad4 AFR exome AF: 0.0659

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0978

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.148 AC: 22610 AN: 152258 Hom.: 2055 Cov.: 32 AF XY: 0.145 AC XY: 10807 AN XY: 74430

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.129

Alfa AF: 0.192 Hom.: 4218

Bravo AF: 0.138

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.97
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2241592; hg19: chr19-8386306; COSMIC: COSV56847820;