1-160813767-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002348.4(LY9):c.586C>A(p.Pro196Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,140 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (13 hom., cov: 32)
  • Exomes 𝑓: 0.016 (217 hom.)
• Consequence: LY9 NM_002348.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.70

Genes affected

LY9 (HGNC:6730): (lymphocyte antigen 9) LY9 belongs to the SLAM family of immunomodulatory receptors (see SLAMF1; MIM 603492) and interacts with the adaptor molecule SAP (SH2D1A; MIM 300490) (Graham et al., 2006 [PubMed 16365421]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028006732).
• BP6: Variant 1-160813767-C-A is Benign according to our data. Variant chr1-160813767-C-A is described in ClinVar as [Benign]. Clinvar id is 783299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0156 (22841/1461874) while in subpopulation NFE AF= 0.0185 (20626/1112000). AF 95% confidence interval is 0.0183. There are 217 homozygotes in gnomad4_exome. There are 10840 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY9	NM_002348.4	c.586C>A	p.Pro196Thr	missense_variant	3/10	ENST00000263285.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY9	ENST00000263285.11	c.586C>A	p.Pro196Thr	missense_variant	3/10	1	NM_002348.4	P2

Frequencies

GnomAD3 genomes AF: 0.00993 AC: 1511 AN: 152148 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00935 AC: 2352 AN: 251454 Hom.: 19 AF XY: 0.00908 AC XY: 1234 AN XY: 135894

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00225

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.0156 AC: 22841 AN: 1461874 Hom.: 217 Cov.: 31 AF XY: 0.0149 AC XY: 10840 AN XY: 727236

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.00539

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00221

Gnomad4 FIN exome AF: 0.0184

Gnomad4 NFE exome AF: 0.0185

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.00992 AC: 1510 AN: 152266 Hom.: 13 Cov.: 32 AF XY: 0.00971 AC XY: 723 AN XY: 74450

Gnomad4 AFR AF: 0.00308

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.0123 Hom.: 15

Bravo AF: 0.00873

TwinsUK AF: 0.0162 AC: 60

ALSPAC AF: 0.0182 AC: 70

ESP6500AA AF: 0.00409 AC: 18

ESP6500EA AF: 0.0155 AC: 133

ExAC AF: 0.00847 AC: 1029

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0152

EpiControl AF: 0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.0010
Dann	Benign	0.23
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.55	T;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.20	T
REVEL	Benign	0.018
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.078
MVP		0.14
MPC		0.072
ClinPred		0.012	T
GERP RS		-8.3
Varity_R		0.055
gMVP		0.30

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: rs35923801; hg19: chr1-160783557;