chr2-3575322-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001011.4(RPS7):​c.-47G>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 0.0000117 in 341,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: RPS7 NM_001011.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000117 AC: 4 AN: 341876 Hom.: 0 Cov.: 0 AF XY: 0.0000165 AC XY: 3 AN XY: 182108

African (AFR) AF: 0.00 AC: 0 AN: 7192

American (AMR) AF: 0.00 AC: 0 AN: 11000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9896

East Asian (EAS) AF: 0.00 AC: 0 AN: 21766

South Asian (SAS) AF: 0.00 AC: 0 AN: 38536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1450

European-Non Finnish (NFE) AF: 0.0000192 AC: 4 AN: 208824

Other (OTH) AF: 0.00 AC: 0 AN: 19566

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 21

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	17
DANN	Benign	0.66
PhyloP100		3.2
PromoterAI		0.093	Neutral
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

Other links and lift over

dbSNP: rs11558965; hg19: chr2-3622912;