chr2-3575322-G-T

Variant names:

• chr2-3575322-G-T
• rs11558965
• NM_001011.4:c.-47G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 VariationId 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.

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.-47G>T		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.-47G>T		5_prime_UTR	Exon 1 of 7	ENSP00000496757.1	P62081
	RPS7	ENST00000646909.1		c.-82G>T		5_prime_UTR	Exon 1 of 7	ENSP00000496654.1	P62081
	RPS7	ENST00000905977.1		c.-38G>T		5_prime_UTR	Exon 1 of 7	ENSP00000576036.1

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

African (AFR) AF: 0.0206 AC: 148 AN: 7190

American (AMR) AF: 0.0415 AC: 456 AN: 10996

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 778 AN: 9872

East Asian (EAS) AF: 0.0578 AC: 1257 AN: 21750

South Asian (SAS) AF: 0.0897 AC: 3454 AN: 38512

European-Finnish (FIN) AF: 0.0399 AC: 943 AN: 23624

Middle Eastern (MID) AF: 0.0815 AC: 118 AN: 1448

European-Non Finnish (NFE) AF: 0.0703 AC: 14658 AN: 208650

Other (OTH) AF: 0.0651 AC: 1273 AN: 19552

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

African (AFR) AF: 0.0195 AC: 810 AN: 41576

American (AMR) AF: 0.0577 AC: 884 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.0602 AC: 311 AN: 5170

South Asian (SAS) AF: 0.0980 AC: 473 AN: 4826

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4823 AN: 68034

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0411 Hom.: 21

Bravo AF: 0.0528

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Diamond-Blackfan anemia 8 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	17
DANN	Benign	0.70
PhyloP100		3.2
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	polymorphism (auto)

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: rs11558965; hg19: chr2-3622912;