rs12692566

chr2-159819916-C-Achr2-159819916-C-Gchr2-159819916-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002349.4(LY75):c.3963G>T(p.Lys1321Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,594,716 control chromosomes in the GnomAD database, including 548,338 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.84 (54310 hom., cov: 32)
  • Exomes 𝑓: 0.83 (494028 hom.)
• Consequence: LY75 NM_002349.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517

Genes affected

LY75 (HGNC:6729): (lymphocyte antigen 75) Predicted to enable signaling receptor activity. Predicted to be involved in immune response and inflammatory response. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LY75-CD302 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3575503E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY75	NM_002349.4	c.3963G>T	p.Lys1321Asn	missense_variant	29/35	ENST00000263636.5
LY75-CD302	NM_001198760.1	c.3963G>T	p.Lys1321Asn	missense_variant	29/38
LY75-CD302	NM_001198759.1	c.3963G>T	p.Lys1321Asn	missense_variant	29/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY75	ENST00000263636.5	c.3963G>T	p.Lys1321Asn	missense_variant	29/35	1	NM_002349.4	P1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128269 AN: 152050 Hom.: 54252 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.845

GnomAD3 exomes AF: 0.826 AC: 193416 AN: 234094 Hom.: 80185 AF XY: 0.819 AC XY: 103768 AN XY: 126704

Gnomad AFR exome AF: 0.885

Gnomad AMR exome AF: 0.878

Gnomad ASJ exome AF: 0.830

Gnomad EAS exome AF: 0.898

Gnomad SAS exome AF: 0.731

Gnomad FIN exome AF: 0.793

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.827

GnomAD4 exome AF: 0.827 AC: 1192413 AN: 1442550 Hom.: 494028 Cov.: 44 AF XY: 0.823 AC XY: 590132 AN XY: 717100

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 0.911

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.795

Gnomad4 NFE exome AF: 0.829

Gnomad4 OTH exome AF: 0.826

GnomAD4 genome AF: 0.844 AC: 128392 AN: 152166 Hom.: 54310 Cov.: 32 AF XY: 0.840 AC XY: 62503 AN XY: 74366

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.847

Alfa AF: 0.829 Hom.: 122364

Bravo AF: 0.857

TwinsUK AF: 0.843 AC: 3125

ALSPAC AF: 0.823 AC: 3172

ESP6500AA AF: 0.890 AC: 3915

ESP6500EA AF: 0.828 AC: 7118

ExAC AF: 0.824 AC: 99962

Asia WGS AF: 0.842 AC: 2926 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	11
Dann	Benign	0.40
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.17	T;T;T
MetaRNN	Benign	8.4e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	1.9	N;N;N
REVEL	Benign	0.071
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.053
MutPred		0.56		Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);Loss of ubiquitination at K1321 (P = 0.0155);
MPC		0.055
ClinPred		0.0061	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.33

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: rs12692566; hg19: chr2-160676427; COSMIC: COSV55102106;