NM_006863.4:c.616C>T

Variant names:

• chr19-54595357-C-T
• rs150400481
• NM_006863.4:c.616C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006863.4(LILRA1):​c.616C>T​(p.His206Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRA1 NM_006863.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 2 publications found

Genes affected

LILRA1 (HGNC:6602): (leukocyte immunoglobulin like receptor A1) This gene encodes an activating member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein is predominantly expressed in B cells, interacts with major histocompatibility complex class I ligands, and contributes to the regulation of immune responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038981438).
• BP6: Variant 19-54595357-C-T is Benign according to our data. Variant chr19-54595357-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3118732.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006863.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA1	NM_006863.4	MANE Select	c.616C>T	p.His206Tyr	missense	Exon 5 of 10	NP_006854.1	O75019-1
	LILRA1	NM_001278319.1		c.616C>T	p.His206Tyr	missense	Exon 4 of 7	NP_001265248.1	O75019
	LILRA1	NM_001278318.2		c.616C>T	p.His206Tyr	missense	Exon 5 of 8	NP_001265247.1	O75019-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRA1	ENST00000251372.8	TSL:1 MANE Select	c.616C>T	p.His206Tyr	missense	Exon 5 of 10	ENSP00000251372.3	O75019-1
	LILRA1	ENST00000453777.1	TSL:1	c.616C>T	p.His206Tyr	missense	Exon 5 of 8	ENSP00000413715.1	O75019-2
	LILRA1	ENST00000473156.5	TSL:1	n.782C>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 1688 AN: 88082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0122

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00895

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.00872

Gnomad MID AF: 0.00450

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0182

GnomAD2 exomes AF: 0.000386 AC: 97 AN: 250996 AF XY: 0.000369

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00399

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000490

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000235 AC: 332 AN: 1411476 Hom.: 1 Cov.: 87 AF XY: 0.000236 AC XY: 166 AN XY: 703052

African (AFR) AF: 0.00126 AC: 40 AN: 31852

American (AMR) AF: 0.000525 AC: 23 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.00427 AC: 108 AN: 25302

East Asian (EAS) AF: 0.000103 AC: 4 AN: 38720

South Asian (SAS) AF: 0.000110 AC: 9 AN: 81760

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52620

Middle Eastern (MID) AF: 0.000365 AC: 2 AN: 5472

European-Non Finnish (NFE) AF: 0.000103 AC: 111 AN: 1073648

Other (OTH) AF: 0.000583 AC: 34 AN: 58332

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0192 AC: 1688 AN: 88140 Hom.: 0 Cov.: 32 AF XY: 0.0206 AC XY: 895 AN XY: 43446

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0248 AC: 542 AN: 21890

American (AMR) AF: 0.0146 AC: 137 AN: 9388

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 44 AN: 1624

East Asian (EAS) AF: 0.00897 AC: 35 AN: 3904

South Asian (SAS) AF: 0.0699 AC: 183 AN: 2618

European-Finnish (FIN) AF: 0.00872 AC: 65 AN: 7456

Middle Eastern (MID) AF: 0.00500 AC: 1 AN: 200

European-Non Finnish (NFE) AF: 0.0166 AC: 651 AN: 39292

Other (OTH) AF: 0.0188 AC: 24 AN: 1276

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.102 Hom.: 3193

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000354 AC: 43

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.087
DANN	Benign	0.65
DEOGEN2	Benign	0.00036	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00073	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-2.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.0090
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.089
MVP		0.040
MPC		0.025
ClinPred		0.0014	T
GERP RS		-2.0
Varity_R		0.029
gMVP		0.022
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150400481; hg19: chr19-55106822; COSMIC: COSV105087163;