rs3740254

Variant names:

• chr10-78033793-A-G
• rs3740254
• ENST00000435275.5:c.-109A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-78033793-A-G
• chr10-78033793-A-C
• chr10-78033793-A-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000435275.5(RPS24):​c.-109A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,498,660 control chromosomes in the GnomAD database, including 2,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (343 hom., cov: 32)
  • Exomes 𝑓: 0.041 (2548 hom.)
• Consequence: RPS24 ENST00000435275.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.363
• Publications: 7 publications found

Genes affected

RPS24 (HGNC:10411): (ribosomal protein S24) 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 S24E family of ribosomal proteins. It is located in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Mutations in this gene result in Diamond-Blackfan anemia. [provided by RefSeq, Nov 2008]

RPS24 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia

  Inheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Diamond-Blackfan anemia 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 10-78033793-A-G is Benign according to our data. Variant chr10-78033793-A-G is described in ClinVar as Benign. ClinVar VariationId is 301088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435275.5. 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
	RPS24	NM_033022.4	MANE Select	c.-109A>G		upstream_gene	N/A	NP_148982.1	P62847-2
	RPS24	NM_001142285.2		c.-109A>G		upstream_gene	N/A	NP_001135757.1	P62847-4
	RPS24	NM_001026.5		c.-109A>G		upstream_gene	N/A	NP_001017.1	P62847-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS24	ENST00000435275.5	TSL:2	c.-109A>G		5_prime_UTR	Exon 1 of 6	ENSP00000415549.1	E7ETK0
	RPS24	ENST00000613865.5	TSL:5	c.-109A>G		5_prime_UTR	Exon 1 of 5	ENSP00000478869.2	P62847-1
	RPS24	ENST00000913449.1		c.-109A>G		5_prime_UTR	Exon 1 of 6	ENSP00000583508.1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6948 AN: 152110 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.0415 AC: 55864 AN: 1346432 Hom.: 2548 Cov.: 21 AF XY: 0.0438 AC XY: 29627 AN XY: 675988

African (AFR) AF: 0.0298 AC: 931 AN: 31224

American (AMR) AF: 0.0961 AC: 4283 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 270 AN: 25436

East Asian (EAS) AF: 0.215 AC: 8414 AN: 39144

South Asian (SAS) AF: 0.135 AC: 11319 AN: 84062

European-Finnish (FIN) AF: 0.0345 AC: 1782 AN: 51712

Middle Eastern (MID) AF: 0.0244 AC: 136 AN: 5566

European-Non Finnish (NFE) AF: 0.0257 AC: 25866 AN: 1008040

Other (OTH) AF: 0.0505 AC: 2863 AN: 56692

GnomAD4 genome AF: 0.0457 AC: 6961 AN: 152228 Hom.: 343 Cov.: 32 AF XY: 0.0503 AC XY: 3741 AN XY: 74412

African (AFR) AF: 0.0303 AC: 1260 AN: 41544

American (AMR) AF: 0.0963 AC: 1473 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 39 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1215 AN: 5154

South Asian (SAS) AF: 0.156 AC: 751 AN: 4822

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0256 AC: 1742 AN: 68010

Other (OTH) AF: 0.0506 AC: 107 AN: 2116

Alfa AF: 0.0131 Hom.: 4

Bravo AF: 0.0469

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Diamond-Blackfan anemia (1)
-	-	1	Diamond-Blackfan anemia 3 (1)
-	-	1	not provided (1)
-	-	1	POLR-related leukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.36
PromoterAI		-0.078	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3740254; hg19: chr10-79793551; COSMIC: COSV62602305; COSMIC: COSV62602305;