17-8377741-A-C

Position:

• chr17-8377741-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000987.5(RPL26):​c.310-49T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,549,132 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (145 hom.)
• Consequence: RPL26 NM_000987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.592

Genes affected

RPL26 (HGNC:10327): (ribosomal protein L26) 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 60S subunit. The protein belongs to the L24P 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. Mutations in this gene result in Diamond-Blackfan anemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-8377741-A-C is Benign according to our data. Variant chr17-8377741-A-C is described in ClinVar as [Benign]. Clinvar id is 1277419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL26	NM_000987.5	c.310-49T>G		intron_variant		ENST00000648839.1
RPL26	NM_001315530.2	c.310-49T>G		intron_variant
RPL26	NM_001315531.2	c.310-49T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL26	ENST00000648839.1	c.310-49T>G		intron_variant			NM_000987.5	P1
	ENST00000666354.1	n.154-3304A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 538 AN: 152184 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.0107 AC: 2393 AN: 223090 Hom.: 77 AF XY: 0.00836 AC XY: 1021 AN XY: 122172

Gnomad AFR exome AF: 0.000544

Gnomad AMR exome AF: 0.0644

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0318

Gnomad SAS exome AF: 0.00151

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000380

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00305 AC: 4254 AN: 1396830 Hom.: 145 Cov.: 24 AF XY: 0.00278 AC XY: 1927 AN XY: 692448

Gnomad4 AFR exome AF: 0.000540

Gnomad4 AMR exome AF: 0.0563

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0459

Gnomad4 SAS exome AF: 0.00163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000242

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00353 AC: 537 AN: 152302 Hom.: 12 Cov.: 33 AF XY: 0.00393 AC XY: 293 AN XY: 74482

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0295

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00181 Hom.: 2

Bravo AF: 0.00643

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs79285623; hg19: chr17-8281059;