19-54369204-T-C

Variant names:

• chr19-54369204-T-C
• rs11084332
• ENST00000438193.1:c.16+1058A>G

Variant summary

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

The ENST00000438193.1(LAIR1):​c.16+1058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,016 control chromosomes in the GnomAD database, including 9,321 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 0.32 (9321 hom., cov: 31)
• Consequence: LAIR1 ENST00000438193.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974
• Publications: 12 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438193.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR1	NM_001289026.3		c.16+1058A>G		intron	N/A	NP_001275955.2
	LAIR1	NM_001289027.3		c.16+1058A>G		intron	N/A	NP_001275956.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAIR1	ENST00000438193.1	TSL:1	c.16+1058A>G		intron	N/A	ENSP00000392058.1
	LAIR1	ENST00000391743.7	TSL:2	c.16+1058A>G		intron	N/A	ENSP00000375623.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48559 AN: 150900 Hom.: 9323 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.322 AC: 48572 AN: 151016 Hom.: 9321 Cov.: 31 AF XY: 0.325 AC XY: 23977 AN XY: 73822

African (AFR) AF: 0.138 AC: 5618 AN: 40602

American (AMR) AF: 0.280 AC: 4267 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1871 AN: 3456

East Asian (EAS) AF: 0.301 AC: 1551 AN: 5156

South Asian (SAS) AF: 0.398 AC: 1897 AN: 4772

European-Finnish (FIN) AF: 0.393 AC: 4132 AN: 10512

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27960 AN: 67958

Other (OTH) AF: 0.352 AC: 740 AN: 2104

Alfa AF: 0.391 Hom.: 22047

Bravo AF: 0.304

Asia WGS AF: 0.316 AC: 1094 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		0.97
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: rs11084332; hg19: chr19-54880811;