Genetic Variant RPS7:c.-36A>C (chr2-3575333-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Publications

1 publications found

Variant links:

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

RPS7 links:

ENSG00000287126 (HGNC:):

ENSG00000287126 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00403

AC XY:

789

AN XY:

195588

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

7828

American (AMR)

AF:

0.00

AC:

AN:

12306

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

10618

East Asian (EAS)

AF:

0.0583

AC:

1386

AN:

23794

South Asian (SAS)

AF:

0.00113

AC:

AN:

40778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25092

Middle Eastern (MID)

AF:

0.00127

AC:

AN:

1580

European-Non Finnish (NFE)

AF:

0.0000940

AC:

AN:

223288

Other (OTH)

AF:

0.00255

AC:

AN:

20778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

129

193

258

322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00237

AC:

361

AN:

152286

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0642

AC:

331

AN:

5156

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.00301

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diamond-Blackfan anemia 8 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

1.4

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over