ENST00000438193.1:c.16+1058A>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAIR1	NM_001289026.3	c.16+1058A>G		intron_variant	Intron 1 of 9		NP_001275955.2
LAIR1	NM_001289027.3	c.16+1058A>G		intron_variant	Intron 1 of 8		NP_001275956.2
LAIR1	XM_047438810.1	c.16+1058A>G		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.16+1058A>G		intron_variant	Intron 1 of 2	1		ENSP00000392058.1
LAIR1	ENST00000391743.7	c.16+1058A>G		intron_variant	Intron 1 of 8	2		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

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.352

Alfa AF: 0.402 Hom.: 15902

Bravo AF: 0.304

Asia WGS AF: 0.316 AC: 1094 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11084332; hg19: chr19-54880811;