1-160799900-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002348.4(LY9):c.272G>A(p.Arg91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,614,114 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R91C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (26 hom.)
• Consequence: LY9 NM_002348.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.85

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038803518).
• BP6: Variant 1-160799900-G-A is Benign according to our data. Variant chr1-160799900-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY9	NM_002348.4	c.272G>A	p.Arg91His	missense_variant	2/10	ENST00000263285.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY9	ENST00000263285.11	c.272G>A	p.Arg91His	missense_variant	2/10	1	NM_002348.4	P2

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 428 AN: 152126 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00501

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00258 AC: 649 AN: 251486 Hom.: 2 AF XY: 0.00248 AC XY: 337 AN XY: 135918

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000924

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00466

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00402 AC: 5880 AN: 1461870 Hom.: 26 Cov.: 31 AF XY: 0.00380 AC XY: 2761 AN XY: 727236

Gnomad4 AFR exome AF: 0.000806

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000579

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.00490

Gnomad4 OTH exome AF: 0.00306

GnomAD4 genome AF: 0.00281 AC: 428 AN: 152244 Hom.: 1 Cov.: 32 AF XY: 0.00244 AC XY: 182 AN XY: 74448

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00501

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00417 Hom.: 1

Bravo AF: 0.00255

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00265 AC: 322

EpiCase AF: 0.00403

EpiControl AF: 0.00415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

LY9-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.0030
Dann	Benign	0.47
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.43	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0039	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.20	T
REVEL	Benign	0.020
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.079
MVP		0.41
MPC		0.072
ClinPred		0.010	T
GERP RS		-8.1
Varity_R		0.016
gMVP		0.18

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: rs35759983; hg19: chr1-160769690; COSMIC: COSV54432389; COSMIC: COSV54432389;