chr1-153991332-C-T

Variant names:

• chr1-153991332-C-T
• rs41265213
• NM_001030.6:c.115+109C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001030.6(RPS27):​c.115+109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,520,826 control chromosomes in the GnomAD database, including 1,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (99 hom., cov: 32)
  • Exomes 𝑓: 0.035 (988 hom.)
• Consequence: RPS27 NM_001030.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0910
• Publications: 1 publications found

Genes affected

RPS27 (HGNC:10416): (ribosomal protein S27) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the S27e family of ribosomal proteins and component of the 40S subunit. The encoded protein contains a C4-type zinc finger domain that can bind to zinc and may bind to nucleic acid. Mutations in this gene have been identified in numerous melanoma patients and in at least one patient with Diamond-Blackfan anemia (DBA). Elevated expression of this gene has been observed in various human cancers. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2018]

RPS27 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 17

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-153991332-C-T is Benign according to our data. Variant chr1-153991332-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0287 (4372/152218) while in subpopulation NFE AF = 0.0392 (2668/68010). AF 95% confidence interval is 0.038. There are 99 homozygotes in GnomAd4. There are 2250 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4372 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030.6. 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
	RPS27	NM_001030.6	MANE Select	c.115+109C>T		intron	N/A	NP_001021.1	P42677
	RPS27	NM_001349946.2		c.19+109C>T		intron	N/A	NP_001336875.1
	RPS27	NM_001349947.2		c.19+109C>T		intron	N/A	NP_001336876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS27	ENST00000651669.1	MANE Select	c.115+109C>T		intron	N/A	ENSP00000499044.1	P42677
	RPS27	ENST00000936806.1		c.238+109C>T		intron	N/A	ENSP00000606865.1
	RPS27	ENST00000936804.1		c.236+109C>T		intron	N/A	ENSP00000606863.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4373 AN: 152102 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0798

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0301 AC: 4018 AN: 133320 AF XY: 0.0291

Gnomad AFR exome AF: 0.00633

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0333

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0851

Gnomad NFE exome AF: 0.0357

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0349 AC: 47827 AN: 1368608 Hom.: 988 Cov.: 31 AF XY: 0.0343 AC XY: 23092 AN XY: 673928

African (AFR) AF: 0.00540 AC: 160 AN: 29616

American (AMR) AF: 0.0164 AC: 439 AN: 26828

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 888 AN: 23740

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35510

South Asian (SAS) AF: 0.00568 AC: 429 AN: 75582

European-Finnish (FIN) AF: 0.0811 AC: 3929 AN: 48450

Middle Eastern (MID) AF: 0.00478 AC: 23 AN: 4808

European-Non Finnish (NFE) AF: 0.0376 AC: 40147 AN: 1067574

Other (OTH) AF: 0.0321 AC: 1811 AN: 56500

GnomAD4 genome AF: 0.0287 AC: 4372 AN: 152218 Hom.: 99 Cov.: 32 AF XY: 0.0302 AC XY: 2250 AN XY: 74402

African (AFR) AF: 0.00606 AC: 252 AN: 41556

American (AMR) AF: 0.0248 AC: 379 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.0798 AC: 843 AN: 10566

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2668 AN: 68010

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0332 Hom.: 179

Bravo AF: 0.0228

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		-0.091
Mutation Taster		=100/0	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: rs41265213; hg19: chr1-153963808; COSMIC: COSV55153272;