ENST00000449223.3:n.326C>T

Variant names:

• chr19-8321483-C-T
• rs2241591
• ENST00000449223.3:n.326C>T

Variant summary

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

The ENST00000449223.3(RPS28):​n.326C>T 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 0.0972 in 1,549,990 control chromosomes in the GnomAD database, including 7,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (701 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7003 hom.)
• Consequence: RPS28 ENST00000449223.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.56
• Publications: 11 publications found

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]

ENSG00000167774 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-8321483-C-T is Benign according to our data. Variant chr19-8321483-C-T is described in CliVar as Benign. Clinvar id is 1257584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA7	NM_005001.5	c.-125G>A		upstream_gene_variant		ENST00000301457.3	NP_004992.2
RPS28	NM_001031.5	c.-48C>T		upstream_gene_variant		ENST00000600659.3	NP_001022.1
NDUFA7	NR_135539.2	n.-108G>A		upstream_gene_variant
RPS28	XM_047439201.1	c.-48C>T		upstream_gene_variant			XP_047295157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3	c.-125G>A		upstream_gene_variant		1	NM_005001.5	ENSP00000301457.1
RPS28	ENST00000600659.3	c.-48C>T		upstream_gene_variant		1	NM_001031.5	ENSP00000472469.1
ENSG00000167774	ENST00000598884.1	n.-125G>A		upstream_gene_variant		4		ENSP00000470609.1

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14020 AN: 152096 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0873

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0981

GnomAD2 exomes AF: 0.0911 AC: 14911 AN: 163744 AF XY: 0.0927

Gnomad AFR exome AF: 0.0893

Gnomad AMR exome AF: 0.0458

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.0902

Gnomad NFE exome AF: 0.0954

Gnomad OTH exome AF: 0.0934

GnomAD4 exome AF: 0.0977 AC: 136573 AN: 1397776 Hom.: 7003 Cov.: 33 AF XY: 0.0975 AC XY: 67222 AN XY: 689280

African (AFR) AF: 0.0925 AC: 2962 AN: 32008

American (AMR) AF: 0.0486 AC: 1736 AN: 35714

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 3762 AN: 24178

East Asian (EAS) AF: 0.140 AC: 5156 AN: 36742

South Asian (SAS) AF: 0.0777 AC: 6082 AN: 78238

European-Finnish (FIN) AF: 0.0911 AC: 4428 AN: 48610

Middle Eastern (MID) AF: 0.121 AC: 549 AN: 4554

European-Non Finnish (NFE) AF: 0.0982 AC: 105997 AN: 1079912

Other (OTH) AF: 0.102 AC: 5901 AN: 57820

GnomAD4 genome AF: 0.0922 AC: 14030 AN: 152214 Hom.: 701 Cov.: 32 AF XY: 0.0905 AC XY: 6735 AN XY: 74410

African (AFR) AF: 0.0873 AC: 3628 AN: 41540

American (AMR) AF: 0.0684 AC: 1046 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 573 AN: 3468

East Asian (EAS) AF: 0.140 AC: 722 AN: 5164

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4824

European-Finnish (FIN) AF: 0.0861 AC: 913 AN: 10606

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0946 AC: 6434 AN: 67996

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0931 Hom.: 1464

Bravo AF: 0.0909

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 27, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.25
DANN	Benign	0.80
PhyloP100		-1.6
PromoterAI		0.034	Neutral

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: rs2241591; hg19: chr19-8386367; COSMIC: COSV56846441;