rs16844374

Positions:

• chr2-159829591-T-C

Variant summary

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

The NM_002349.4(LY75):​c.3958+2079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,154 control chromosomes in the GnomAD database, including 2,293 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 0.16 (2293 hom., cov: 33)
• Consequence: LY75 NM_002349.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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:38828): (LY75-CD302 readthrough) This locus represents naturally occurring read-through transcription between the neighboring lymphocyte antigen 75 (LY75) and CD302 molecule (CD302) genes. Alternative splicing results in multiple transcript variants encoding fusion products that share sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY75	NM_002349.4	c.3958+2079A>G		intron_variant		ENST00000263636.5	NP_002340.2
LY75-CD302	NM_001198759.1	c.3958+2079A>G		intron_variant			NP_001185688.1
LY75-CD302	NM_001198760.1	c.3958+2079A>G		intron_variant			NP_001185689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY75	ENST00000263636.5	c.3958+2079A>G		intron_variant		1	NM_002349.4	ENSP00000263636.4
LY75-CD302	ENST00000504764.5	c.3958+2079A>G		intron_variant		2		ENSP00000423463.1
LY75-CD302	ENST00000505052.1	c.3958+2079A>G		intron_variant		2		ENSP00000421035.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24539 AN: 152036 Hom.: 2289 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24568 AN: 152154 Hom.: 2293 Cov.: 33 AF XY: 0.164 AC XY: 12205 AN XY: 74390

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.177

Alfa AF: 0.161 Hom.: 269

Bravo AF: 0.176

Asia WGS AF: 0.243 AC: 842 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.58

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: rs16844374; hg19: chr2-160686102;