14-49620530-T-C

Variant names:

• chr14-49620530-T-C
• rs8018849
• NM_001001.5:c.-37+32A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001.5(RPL36AL):​c.-37+32A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 163,962 control chromosomes in the GnomAD database, including 856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (853 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (3 hom.)
• Consequence: RPL36AL NM_001001.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.99
• Publications: 2 publications found

Genes affected

RPL36AL (HGNC:10346): (ribosomal protein L36a like) Cytoplasmic ribosomes, 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, which shares sequence similarity with yeast ribosomal protein L44, belongs to the L44E (L36AE) family of ribosomal proteins. This gene and the human gene officially named ribosomal protein L36a (RPL36A) encode nearly identical proteins; however, they are distinct genes. Although the name of this gene has been referred to as ribosomal protein L36a (RPL36A), its official name is ribosomal protein L36a-like (RPL36AL). 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]

ENSG00000258377 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 14-49620530-T-C is Benign according to our data. Variant chr14-49620530-T-C is described in ClinVar as Benign. ClinVar VariationId is 1230840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001.5. 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
	RPL36AL	NM_001001.5	MANE Select	c.-37+32A>G		intron	N/A	NP_000992.1	Q969Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL36AL	ENST00000298289.7	TSL:1 MANE Select	c.-37+32A>G		intron	N/A	ENSP00000346012.5	Q969Q0
	RPL36AL	ENST00000936362.1		c.-1265A>G		5_prime_UTR	Exon 1 of 2	ENSP00000606421.1
	RPL36AL	ENST00000936364.1		c.-156A>G		5_prime_UTR	Exon 1 of 2	ENSP00000606423.1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9118 AN: 152174 Hom.: 851 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.0397

GnomAD4 exome AF: 0.00746 AC: 87 AN: 11670 Hom.: 3 Cov.: 0 AF XY: 0.00618 AC XY: 39 AN XY: 6312

African (AFR) AF: 0.180 AC: 46 AN: 256

American (AMR) AF: 0.0127 AC: 10 AN: 788

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 6 AN: 274

East Asian (EAS) AF: 0.00 AC: 0 AN: 224

South Asian (SAS) AF: 0.00 AC: 0 AN: 1774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00190 AC: 14 AN: 7356

Other (OTH) AF: 0.0174 AC: 11 AN: 632

GnomAD4 genome AF: 0.0600 AC: 9131 AN: 152292 Hom.: 853 Cov.: 33 AF XY: 0.0581 AC XY: 4328 AN XY: 74476

African (AFR) AF: 0.201 AC: 8364 AN: 41556

American (AMR) AF: 0.0298 AC: 456 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 68026

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0483 Hom.: 98

Bravo AF: 0.0676

Asia WGS AF: 0.0130 AC: 46 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	-0.66
CADD	Benign	0.24
DANN	Benign	0.46
PhyloP100		-4.0
PromoterAI		-0.030	Neutral
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)		0.020		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: rs8018849; hg19: chr14-50087248;