rs2070764

Variant names:

• chr8-73292418-A-T
• rs2070764
• NM_000971.4:c.124-13T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-73292418-A-T
• chr8-73292418-A-C
• chr8-73292418-A-G

Variant summary

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

The NM_000971.4(RPL7):​c.124-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,586,164 control chromosomes in the GnomAD database, including 121,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.41 (12817 hom., cov: 31)
  • Exomes 𝑓: 0.38 (108482 hom.)
• Consequence: RPL7 NM_000971.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 20 publications found

Genes affected

RPL7 (HGNC:10363): (ribosomal protein L7) 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 L30P family of ribosomal proteins. It contains an N-terminal basic region-leucine zipper (BZIP)-like domain and the RNP consensus submotif RNP2. In vitro the BZIP-like domain mediates homodimerization and stable binding to DNA and RNA, with a preference for 28S rRNA and mRNA. The protein can inhibit cell-free translation of mRNAs, suggesting that it plays a regulatory role in the translation apparatus. It is located in the cytoplasm. The protein has been shown to be an autoantigen in patients with systemic autoimmune diseases, such as systemic lupus erythematosus. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000971.4. 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
	RPL7	NM_000971.4	MANE Select	c.124-13T>A		intron	N/A	NP_000962.2
	RPL7	NM_001363737.2		c.4-13T>A		intron	N/A	NP_001350666.1	A8MUD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL7	ENST00000352983.7	TSL:1 MANE Select	c.124-13T>A		intron	N/A	ENSP00000339795.2	P18124
	RPL7	ENST00000863689.1		c.124-13T>A		intron	N/A	ENSP00000533748.1
	RPL7	ENST00000863690.1		c.124-13T>A		intron	N/A	ENSP00000533749.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61755 AN: 151810 Hom.: 12796 Cov.: 31

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.428 AC: 99409 AN: 231994 AF XY: 0.430

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.507

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.511

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.384 AC: 550603 AN: 1434236 Hom.: 108482 Cov.: 32 AF XY: 0.388 AC XY: 276246 AN XY: 712178

African (AFR) AF: 0.423 AC: 13975 AN: 33008

American (AMR) AF: 0.499 AC: 21547 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 8942 AN: 25830

East Asian (EAS) AF: 0.486 AC: 19181 AN: 39458

South Asian (SAS) AF: 0.541 AC: 45462 AN: 84058

European-Finnish (FIN) AF: 0.456 AC: 18356 AN: 40262

Middle Eastern (MID) AF: 0.371 AC: 2127 AN: 5730

European-Non Finnish (NFE) AF: 0.361 AC: 397687 AN: 1102904

Other (OTH) AF: 0.390 AC: 23326 AN: 59818

GnomAD4 genome AF: 0.407 AC: 61812 AN: 151928 Hom.: 12817 Cov.: 31 AF XY: 0.416 AC XY: 30861 AN XY: 74262

African (AFR) AF: 0.426 AC: 17637 AN: 41422

American (AMR) AF: 0.451 AC: 6894 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2585 AN: 5172

South Asian (SAS) AF: 0.566 AC: 2723 AN: 4812

European-Finnish (FIN) AF: 0.465 AC: 4899 AN: 10534

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24623 AN: 67934

Other (OTH) AF: 0.362 AC: 764 AN: 2108

Alfa AF: 0.286 Hom.: 1115

Bravo AF: 0.403

Asia WGS AF: 0.536 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.017
DANN	Benign	0.57
PhyloP100		-2.8
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2070764; hg19: chr8-74204653; COSMIC: COSV53581734; COSMIC: COSV53581734;