8-142699871-G-C

Variant names:

• chr8-142699871-G-C
• rs2585175
• NM_017527.4:c.-657G>C

Variant summary

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

The NM_017527.4(LY6K):​c.-657G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,710 control chromosomes in the GnomAD database, including 19,164 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 0.50 (19164 hom., cov: 30)
• Consequence: LY6K NM_017527.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

Genes affected

LY6K (HGNC:24225): (lymphocyte antigen 6 family member K) Predicted to be involved in binding activity of sperm to zona pellucida. Predicted to act upstream of or within flagellated sperm motility. Predicted to be located in cell surface; cytoplasm; and plasma membrane. Predicted to be active in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902032 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6K	NM_017527.4	c.-657G>C		upstream_gene_variant		ENST00000292430.10	NP_059997.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6K	ENST00000292430.10	c.-657G>C		upstream_gene_variant		1	NM_017527.4	ENSP00000292430.6
LY6K	ENST00000519387.1	c.-657G>C		upstream_gene_variant		2		ENSP00000429695.1
LY6K	ENST00000518841.5	c.-657G>C		upstream_gene_variant		2		ENSP00000427749.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75745 AN: 151590 Hom.: 19161 Cov.: 30

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.500 AC: 75785 AN: 151710 Hom.: 19164 Cov.: 30 AF XY: 0.497 AC XY: 36833 AN XY: 74116

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.490

Alfa AF: 0.479 Hom.: 2177

Bravo AF: 0.502

Asia WGS AF: 0.437 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2585175; hg19: chr8-143781289;