Genetic Variant KLRD1:c.-134A>T (chr12-10307944-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002262.5(KLRD1):c.-134A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 780,232 control chromosomes in the GnomAD database, including 145,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.56 ( 24677 hom., cov: 32)

Exomes 𝑓: 0.62 ( 121083 hom. )

Consequence

KLRD1
NM_002262.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

10 publications found

Variant links:

Genes affected

KLRD1 (HGNC:6378): (killer cell lectin like receptor D1) Natural killer (NK) cells are a distinct lineage of lymphocytes that mediate cytotoxic activity and secrete cytokines upon immune stimulation. Several genes of the C-type lectin superfamily, including members of the NKG2 family, are expressed by NK cells and may be involved in the regulation of NK cell function. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

KLRD1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002262.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLRD1	NM_002262.5	MANE Select	c.-134A>T	5_prime_UTR	Exon 1 of 6	NP_002253.2	Q13241-1
KLRD1	NM_001414224.1		c.-134A>T	5_prime_UTR	Exon 1 of 7	NP_001401153.1
KLRD1	NM_001351063.2		c.-134A>T	5_prime_UTR	Exon 1 of 5	NP_001337992.1	F6WZH4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLRD1	ENST00000336164.9	TSL:1 MANE Select	c.-134A>T	5_prime_UTR	Exon 1 of 6	ENSP00000338130.4	Q13241-1
KLRD1	ENST00000350274.9	TSL:1	c.-134A>T	5_prime_UTR	Exon 1 of 5	ENSP00000310929.7	Q13241-3
KLRD1	ENST00000381908.7	TSL:1	c.-100-34A>T	intron	N/A	ENSP00000371333.4	Q13241-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

84951

AN:

151808

Hom.:

24673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.587

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.643

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.617

AC:

387481

AN:

628306

Hom.:

121083

Cov.:

AF XY:

0.622

AC XY:

208372

AN XY:

335196

show subpopulations

African (AFR)

AF:

0.394

AC:

6328

AN:

16066

American (AMR)

AF:

0.550

AC:

15771

AN:

28686

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

12017

AN:

17962

East Asian (EAS)

AF:

0.413

AC:

14383

AN:

34866

South Asian (SAS)

AF:

0.659

AC:

39309

AN:

59686

European-Finnish (FIN)

AF:

0.595

AC:

27006

AN:

45370

Middle Eastern (MID)

AF:

0.662

AC:

2623

AN:

3960

European-Non Finnish (NFE)

AF:

0.642

AC:

249984

AN:

389522

Other (OTH)

AF:

0.623

AC:

20060

AN:

32188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6990

13980

20969

27959

34949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2818

5636

8454

11272

14090

<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:

0.559

AC:

84980

AN:

151926

Hom.:

24677

Cov.:

AF XY:

0.558

AC XY:

41444

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.395

AC:

16362

AN:

41392

American (AMR)

AF:

0.570

AC:

8698

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2331

AN:

3468

East Asian (EAS)

AF:

0.453

AC:

2344

AN:

5176

South Asian (SAS)

AF:

0.669

AC:

3228

AN:

4824

European-Finnish (FIN)

AF:

0.587

AC:

6193

AN:

10558

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.643

AC:

43674

AN:

67932

Other (OTH)

AF:

0.597

AC:

1261

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1829

3659

5488

7318

9147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.494

Hom.:

1530

Bravo

AF:

0.551

Asia WGS

AF:

0.563

AC:

1959

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.0

(source)

DANN

Benign

0.56

PhyloP100

-0.086

PromoterAI

0.019

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

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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