6-30553360-G-A

Variant names:

• chr6-30553360-G-A
• rs2074505
• NM_005275.5:c.798C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005275.5(GNL1):​c.798C>T​(p.Asp266Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,609,648 control chromosomes in the GnomAD database, including 360,056 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 0.66 (33272 hom., cov: 31)
  • Exomes 𝑓: 0.67 (326784 hom.)
• Consequence: GNL1 NM_005275.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 27 publications found

Genes affected

GNL1 (HGNC:4413): (G protein nucleolar 1 (putative)) The GNL1 gene, identified in the human major histocompatibility complex class I region, shows a high degree of similarity with its mouse counterpart. The GNL1 gene is located less than 2 kb centromeric to HLA-E, in the same transcriptional orientation. GNL1 is telomeric to HLA-B and HLA-C. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.108 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNL1	NM_005275.5	c.798C>T	p.Asp266Asp	synonymous_variant	Exon 6 of 12	ENST00000376621.8	NP_005266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNL1	ENST00000376621.8	c.798C>T	p.Asp266Asp	synonymous_variant	Exon 6 of 12	1	NM_005275.5	ENSP00000365806.3
GNL1	ENST00000433809.1	c.792C>T	p.Asp264Asp	splice_region_variant, synonymous_variant	Exon 5 of 5	2		ENSP00000404728.1
GNL1	ENST00000487166.1	n.-240C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100331 AN: 151806 Hom.: 33240 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.650

GnomAD2 exomes AF: 0.667 AC: 164730 AN: 246998 AF XY: 0.675

Gnomad AFR exome AF: 0.665

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.770

Gnomad EAS exome AF: 0.661

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.658

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.668 AC: 973671 AN: 1457724 Hom.: 326784 Cov.: 37 AF XY: 0.672 AC XY: 487548 AN XY: 725286

African (AFR) AF: 0.673 AC: 22492 AN: 33406

American (AMR) AF: 0.592 AC: 26469 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 20348 AN: 26126

East Asian (EAS) AF: 0.641 AC: 25459 AN: 39688

South Asian (SAS) AF: 0.765 AC: 65947 AN: 86172

European-Finnish (FIN) AF: 0.665 AC: 34811 AN: 52322

Middle Eastern (MID) AF: 0.742 AC: 3695 AN: 4982

European-Non Finnish (NFE) AF: 0.660 AC: 733185 AN: 1110096

Other (OTH) AF: 0.685 AC: 41265 AN: 60210

GnomAD4 genome AF: 0.661 AC: 100406 AN: 151924 Hom.: 33272 Cov.: 31 AF XY: 0.660 AC XY: 49017 AN XY: 74260

African (AFR) AF: 0.671 AC: 27785 AN: 41388

American (AMR) AF: 0.591 AC: 9029 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3367 AN: 5166

South Asian (SAS) AF: 0.758 AC: 3652 AN: 4820

European-Finnish (FIN) AF: 0.672 AC: 7084 AN: 10538

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44511 AN: 67958

Other (OTH) AF: 0.648 AC: 1370 AN: 2114

Alfa AF: 0.659 Hom.: 128817

Bravo AF: 0.655

Asia WGS AF: 0.669 AC: 2329 AN: 3478

EpiCase AF: 0.674

EpiControl AF: 0.670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		-0.11
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: rs2074505; hg19: chr6-30521137; COSMIC: COSV64835439; COSMIC: COSV64835439;