chr2-3575322-G-T

Position:

• chr2-3575322-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001011.4(RPS7):​c.-47G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 493,910 control chromosomes in the GnomAD database, including 1,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (284 hom., cov: 33)
  • Exomes 𝑓: 0.068 (890 hom.)
• Consequence: RPS7 NM_001011.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.21

Genes affected

RPS7 (HGNC:10440): (ribosomal protein S7) 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 S7E 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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-3575322-G-T is Benign according to our data. Variant chr2-3575322-G-T is described in ClinVar as [Benign]. Clinvar id is 335895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS7	NM_001011.4	c.-47G>T		5_prime_UTR_variant	1/7	ENST00000645674.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS7	ENST00000645674.2	c.-47G>T		5_prime_UTR_variant	1/7		NM_001011.4	P1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8247 AN: 152198 Hom.: 283 Cov.: 33

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.0600

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0714

GnomAD4 exome AF: 0.0676 AC: 23085 AN: 341594 Hom.: 890 Cov.: 0 AF XY: 0.0697 AC XY: 12680 AN XY: 181966

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.0415

Gnomad4 ASJ exome AF: 0.0788

Gnomad4 EAS exome AF: 0.0578

Gnomad4 SAS exome AF: 0.0897

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0703

Gnomad4 OTH exome AF: 0.0651

GnomAD4 genome AF: 0.0541 AC: 8243 AN: 152316 Hom.: 284 Cov.: 33 AF XY: 0.0532 AC XY: 3960 AN XY: 74478

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0577

Gnomad4 ASJ AF: 0.0760

Gnomad4 EAS AF: 0.0602

Gnomad4 SAS AF: 0.0980

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0410 Hom.: 21

Bravo AF: 0.0528

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 06, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Diamond-Blackfan anemia 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	17
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11558965; hg19: chr2-3622912;