rs4817639

Positions:

• chr21-34308001-T-C
• chr21-34308001-T-G
• chr21-34308001-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.817 in 152,162 control chromosomes in the GnomAD database, including 50,948 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 0.82 (50948 hom., cov: 32)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

(HGNC:):

ENSG00000272657 (HGNC:14051): (mitochondrial ribosomal protein S6) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.34308001T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.513+14245T>C		intron_variant		3		ENSP00000520522.1
ENSG00000214955	ENST00000427022.1	n.506+14245T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124169 AN: 152044 Hom.: 50900 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.807

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.817 AC: 124278 AN: 152162 Hom.: 50948 Cov.: 32 AF XY: 0.823 AC XY: 61188 AN XY: 74388

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.809

Alfa AF: 0.795 Hom.: 46442

Bravo AF: 0.816

Asia WGS AF: 0.942 AC: 3275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4817639; hg19: chr21-35680301;