rs56802430

Variant names:

• chr19-54366807-A-G
• rs56802430
• ENST00000438193.1:c.17-2477T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000438193.1(LAIR1):​c.17-2477T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,214 control chromosomes in the GnomAD database, including 2,371 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 0.12 (2371 hom., cov: 32)
• Consequence: LAIR1 ENST00000438193.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 5 publications found

Genes affected

LAIR1 (HGNC:6477): (leukocyte associated immunoglobulin like receptor 1) The protein encoded by this gene is an inhibitory receptor found on peripheral mononuclear cells, including natural killer cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells recognized as self. The gene is a member of both the immunoglobulin superfamily and the leukocyte-associated inhibitory receptor family. The gene maps to a region of 19q13.4 called the leukocyte receptor cluster, which contains at least 29 genes encoding leukocyte-expressed receptors of the immunoglobulin superfamily. The encoded protein has been identified as an anchor for tyrosine phosphatase SHP-1, and may induce cell death in myeloid leukemias. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR1	NM_001289026.3	c.17-2477T>C		intron_variant	Intron 1 of 9		NP_001275955.2
LAIR1	NM_001289027.3	c.16+3455T>C		intron_variant	Intron 1 of 8		NP_001275956.2
LAIR1	XM_047438810.1	c.17-2477T>C		intron_variant	Intron 2 of 10		XP_047294766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAIR1	ENST00000438193.1	c.17-2477T>C		intron_variant	Intron 1 of 2	1		ENSP00000392058.1
LAIR1	ENST00000391743.7	c.16+3455T>C		intron_variant	Intron 1 of 8	2		ENSP00000375623.3
LAIR1	ENST00000480122.1	n.288+1505T>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18184 AN: 152096 Hom.: 2367 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.00866

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.120 AC: 18211 AN: 152214 Hom.: 2371 Cov.: 32 AF XY: 0.119 AC XY: 8823 AN XY: 74452

African (AFR) AF: 0.308 AC: 12802 AN: 41506

American (AMR) AF: 0.148 AC: 2258 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0870 AC: 302 AN: 3470

East Asian (EAS) AF: 0.177 AC: 913 AN: 5172

South Asian (SAS) AF: 0.0836 AC: 403 AN: 4822

European-Finnish (FIN) AF: 0.00866 AC: 92 AN: 10618

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0174 AC: 1182 AN: 68030

Other (OTH) AF: 0.109 AC: 231 AN: 2112

Alfa AF: 0.0406 Hom.: 205

Bravo AF: 0.140

Asia WGS AF: 0.153 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.41
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs56802430; hg19: chr19-54878414;