chr19-54819844-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013289.4(KIR3DL1):c.487G>A(p.Asp163Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00655 in 1,611,838 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 164 hom. )

Consequence

KIR3DL1
NM_013289.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.39

Publications

1 publications found

Variant links:

Genes affected

KIR3DL1 (HGNC:6338): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]

KIR3DL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059251487).

BP6

Variant 19-54819844-G-A is Benign according to our data. Variant chr19-54819844-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2650484.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013289.4. 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
	KIR3DL1	NM_013289.4	MANE Select	c.487G>A	p.Asp163Asn	missense	Exon 4 of 9	NP_037421.2	Q5UCE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIR3DL1	ENST00000391728.8	TSL:1 MANE Select	c.487G>A	p.Asp163Asn	missense	Exon 4 of 9	ENSP00000375608.4	P43629-1
KIR3DL1	ENST00000326542.11	TSL:1	c.487G>A	p.Asp163Asn	missense	Exon 4 of 8	ENSP00000326868.7	W5QJC1
KIR3DL1	ENST00000358178.4	TSL:1	c.202G>A	p.Asp68Asn	missense	Exon 3 of 8	ENSP00000350901.4	P43629-2

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

758

AN:

151430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00151

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.00480

Gnomad ASJ

AF:

0.00232

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000842

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.00480

GnomAD2 exomes

AF:

0.00

AC:

AN:

236064

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00671

AC:

9804

AN:

1460294

Hom.:

164

Cov.:

AF XY:

0.00630

AC XY:

4574

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33364

American (AMR)

AF:

0.00333

AC:

149

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00262

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00168

AC:

144

AN:

85932

European-Finnish (FIN)

AF:

0.000656

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00811

AC:

9011

AN:

1111312

Other (OTH)

AF:

0.00591

AC:

356

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

506

1011

1517

2022

2528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00500

AC:

758

AN:

151544

Hom.:

Cov.:

AF XY:

0.00460

AC XY:

341

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.00151

AC:

AN:

41102

American (AMR)

AF:

0.00479

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00232

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000842

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00776

AC:

527

AN:

67954

Other (OTH)

AF:

0.00475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00563

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.083

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.80

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0051

M_CAP

Benign

0.00091

MetaRNN

Benign

0.0059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-2.4

PROVEAN

Benign

-1.3

REVEL

Benign

0.011

Sift

Uncertain

0.0010

Sift4G

Benign

0.52

Polyphen

0.055

Vest4

0.077

MutPred

0.26

Loss of ubiquitination at K162 (P = 0.0464)

MVP

0.18

MPC

0.41

ClinPred

0.44

GERP RS

0.29

Varity_R

0.35

gMVP

0.016

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over