Genetic Variant RPS15A:c.214-12_214-10delGTT (chr16-18784832-TAAC-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001019.5(RPS15A):c.214-12_214-10delGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,585,296 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

RPS15A
NM_001019.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.303

Publications

0 publications found

Variant links:

Genes affected

RPS15A (HGNC:10389): (ribosomal protein S15a) 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 S8P 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]

RPS15A Gene-Disease associations (from GenCC):

Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Diamond-Blackfan anemia 20
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

RPS15A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 16-18784832-TAAC-T is Benign according to our data. Variant chr16-18784832-TAAC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2746992.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 24 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001019.5. 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
	RPS15A	NM_001019.5	MANE Select	c.214-12_214-10delGTT		intron	N/A	NP_001010.2
	RPS15A	NM_001030009.2		c.214-12_214-10delGTT		intron	N/A	NP_001025180.1	P62244

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPS15A	ENST00000322989.8	TSL:1 MANE Select	c.214-12_214-10delGTT	intron	N/A	ENSP00000318646.4	P62244
RPS15A	ENST00000563390.5	TSL:1	c.214-12_214-10delGTT	intron	N/A	ENSP00000457000.1	P62244
RPS15A	ENST00000576008.5	TSL:1	n.311-12_311-10delGTT	intron	N/A	ENSP00000459373.1	I3L246

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000220

AC:

AN:

231822

AF XY:

0.000183

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000246

Gnomad ASJ exome

AF:

0.000443

Gnomad EAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000352

GnomAD4 exome

AF:

0.000184

AC:

264

AN:

1433144

Hom.:

AF XY:

0.000174

AC XY:

124

AN XY:

713444

show subpopulations

African (AFR)

AF:

0.000187

AC:

AN:

32100

American (AMR)

AF:

0.000230

AC:

AN:

39092

Ashkenazi Jewish (ASJ)

AF:

0.000356

AC:

AN:

25300

East Asian (EAS)

AF:

0.00249

AC:

AN:

39406

South Asian (SAS)

AF:

0.0000244

AC:

AN:

82030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.000708

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000118

AC:

129

AN:

1096978

Other (OTH)

AF:

0.000118

AC:

AN:

59354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000158

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41516

American (AMR)

AF:

0.000458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000182

Hom.:

Bravo

AF:

0.000223

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000274

EpiControl

AF:

0.000179

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

16-18784832-TAACAAC-TAAC

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