1-92840760-G-A

Position:

• chr1-92840760-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000969.5(RPL5):​c.794+121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 795,566 control chromosomes in the GnomAD database, including 176,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28658 hom., cov: 32)
  • Exomes 𝑓: 0.67 (147532 hom.)
• Consequence: RPL5 NM_000969.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.109

Genes affected

RPL5 (HGNC:10360): (ribosomal protein L5) 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 L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

SNORA66 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-92840760-G-A is Benign according to our data. Variant chr1-92840760-G-A is described in ClinVar as [Benign]. Clinvar id is 298213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPL5	NM_000969.5	c.794+121G>A		intron_variant		ENST00000370321.8	NP_000960.2
DIPK1A	NM_001252273.2	c.474+6423C>T		intron_variant			NP_001239202.1
SNORA66	NR_002444.2	n.42G>A		non_coding_transcript_exon_variant	1/1
RPL5	NR_146333.1	n.853+121G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL5	ENST00000370321.8	c.794+121G>A		intron_variant		1	NM_000969.5	ENSP00000359345.2

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91573 AN: 151864 Hom.: 28651 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.580

GnomAD3 exomes AF: 0.686 AC: 160765 AN: 234464 Hom.: 56766 AF XY: 0.688 AC XY: 88674 AN XY: 128798

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.725

Gnomad EAS exome AF: 0.947

Gnomad SAS exome AF: 0.804

Gnomad FIN exome AF: 0.631

Gnomad NFE exome AF: 0.622

Gnomad OTH exome AF: 0.660

GnomAD4 exome AF: 0.669 AC: 430561 AN: 643584 Hom.: 147532 Cov.: 8 AF XY: 0.675 AC XY: 236348 AN XY: 349904

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.745

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.958

Gnomad4 SAS exome AF: 0.797

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.603 AC: 91616 AN: 151982 Hom.: 28658 Cov.: 32 AF XY: 0.608 AC XY: 45170 AN XY: 74274

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.947

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.584

Alfa AF: 0.625 Hom.: 29997

Bravo AF: 0.598

Asia WGS AF: 0.801 AC: 2782 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Diamond-Blackfan anemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.87

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

LitVar

Other links and lift over

dbSNP: rs10874744; hg19: chr1-93306317; COSMIC: COSV59872888; COSMIC: COSV59872888;