1-92837894-G-T

Variant names:

• chr1-92837894-G-T
• rs6659942
• NM_000969.5:c.705+261G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000969.5(RPL5):​c.705+261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 479,690 control chromosomes in the GnomAD database, including 190,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56513 hom., cov: 33)
  • Exomes 𝑓: 0.90 (133531 hom.)
• Consequence: RPL5 NM_000969.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL5	NM_000969.5	c.705+261G>T		intron_variant	Intron 6 of 7	ENST00000370321.8	NP_000960.2
DIPK1A	NM_001252273.2	c.475-4860C>A		intron_variant	Intron 4 of 4		NP_001239202.1
RPL5	NR_146333.1	n.764+261G>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL5	ENST00000370321.8	c.705+261G>T		intron_variant	Intron 6 of 7	1	NM_000969.5	ENSP00000359345.2

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130578 AN: 152128 Hom.: 56495 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.902 AC: 295446 AN: 327442 Hom.: 133531 AF XY: 0.907 AC XY: 159264 AN XY: 175690

African (AFR) AF: 0.751 AC: 7224 AN: 9622

American (AMR) AF: 0.917 AC: 12847 AN: 14012

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 9339 AN: 9886

East Asian (EAS) AF: 0.967 AC: 19167 AN: 19812

South Asian (SAS) AF: 0.945 AC: 39976 AN: 42310

European-Finnish (FIN) AF: 0.882 AC: 13953 AN: 15812

Middle Eastern (MID) AF: 0.922 AC: 1249 AN: 1354

European-Non Finnish (NFE) AF: 0.893 AC: 175113 AN: 196058

Other (OTH) AF: 0.892 AC: 16578 AN: 18576

GnomAD4 genome AF: 0.858 AC: 130651 AN: 152248 Hom.: 56513 Cov.: 33 AF XY: 0.861 AC XY: 64069 AN XY: 74434

African (AFR) AF: 0.746 AC: 30960 AN: 41508

American (AMR) AF: 0.898 AC: 13733 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3311 AN: 3472

East Asian (EAS) AF: 0.962 AC: 4995 AN: 5192

South Asian (SAS) AF: 0.943 AC: 4549 AN: 4822

European-Finnish (FIN) AF: 0.883 AC: 9360 AN: 10602

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.894 AC: 60810 AN: 68030

Other (OTH) AF: 0.853 AC: 1804 AN: 2116

Alfa AF: 0.847 Hom.: 8084

Bravo AF: 0.852

Asia WGS AF: 0.908 AC: 3159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.9
DANN	Benign	0.45
PhyloP100		0.026
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: rs6659942; hg19: chr1-93303451;