rs17552296

Variant names:

• chr2-3575333-A-C
• rs17552296
• NM_001011.4:c.-36A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-3575333-A-C
• chr2-3575333-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001011.4(RPS7):​c.-36A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 518,348 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (44 hom.)
• Consequence: RPS7 NM_001011.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40
• Publications: 1 publications found

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]

RPS7 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 8

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287126 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-3575333-A-C is Benign according to our data. Variant chr2-3575333-A-C is described in ClinVar as Benign. ClinVar VariationId is 335897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011.4. 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
	RPS7	NM_001011.4	MANE Select	c.-36A>C		5_prime_UTR	Exon 1 of 7	NP_001002.1	P62081

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS7	ENST00000645674.2	MANE Select	c.-36A>C		5_prime_UTR	Exon 1 of 7	ENSP00000496757.1	P62081
	RPS7	ENST00000462576.5	TSL:1	c.-277A>C		5_prime_UTR	Exon 1 of 6	ENSP00000495273.1	P62081
	RPS7	ENST00000403564.5	TSL:2	c.-134A>C		5_prime_UTR	Exon 1 of 7	ENSP00000385018.1	P62081

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 364 AN: 152168 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00420 AC: 1539 AN: 366062 Hom.: 44 Cov.: 0 AF XY: 0.00403 AC XY: 789 AN XY: 195588

African (AFR) AF: 0.000128 AC: 1 AN: 7828

American (AMR) AF: 0.00 AC: 0 AN: 12306

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 30 AN: 10618

East Asian (EAS) AF: 0.0583 AC: 1386 AN: 23794

South Asian (SAS) AF: 0.00113 AC: 46 AN: 40778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25092

Middle Eastern (MID) AF: 0.00127 AC: 2 AN: 1580

European-Non Finnish (NFE) AF: 0.0000940 AC: 21 AN: 223288

Other (OTH) AF: 0.00255 AC: 53 AN: 20778

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152286 Hom.: 10 Cov.: 33 AF XY: 0.00267 AC XY: 199 AN XY: 74462

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.0642 AC: 331 AN: 5156

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.00301

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Diamond-Blackfan anemia 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		1.4
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3
Mutation Taster		=300/0	polymorphism

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: rs17552296; hg19: chr2-3622923;