Genetic Variant KLRD1:c.7+205C>T (chr12-10308289-C-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.7+205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 568,208 control chromosomes in the GnomAD database, including 272,169 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 0.94 ( 67393 hom., cov: 32)

Exomes 𝑓: 0.99 ( 204776 hom. )

Consequence

KLRD1
NM_002262.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.650

Publications

2 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.7+205C>T	intron	N/A	NP_002253.2	Q13241-1
KLRD1	NM_001351060.2		c.7+205C>T	intron	N/A	NP_001337989.1
KLRD1	NM_001414224.1		c.7+205C>T	intron	N/A	NP_001401153.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLRD1	ENST00000336164.9	TSL:1 MANE Select	c.7+205C>T	intron	N/A	ENSP00000338130.4	Q13241-1
KLRD1	ENST00000381908.7	TSL:1	c.7+205C>T	intron	N/A	ENSP00000371333.4	Q13241-1
KLRD1	ENST00000543777.5	TSL:1	c.7+205C>T	intron	N/A	ENSP00000443584.1	F6WZH4

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142343

AN:

152108

Hom.:

67365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.977

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.975

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.951

GnomAD4 exome

AF:

0.991

AC:

412418

AN:

415982

Hom.:

204776

Cov.:

AF XY:

0.993

AC XY:

218779

AN XY:

220314

show subpopulations

African (AFR)

AF:

0.774

AC:

9126

AN:

11798

American (AMR)

AF:

0.984

AC:

17528

AN:

17806

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

12678

AN:

12682

East Asian (EAS)

AF:

1.00

AC:

29068

AN:

29068

South Asian (SAS)

AF:

0.999

AC:

40048

AN:

40070

European-Finnish (FIN)

AF:

1.00

AC:

27230

AN:

27230

Middle Eastern (MID)

AF:

0.993

AC:

1822

AN:

1834

European-Non Finnish (NFE)

AF:

0.999

AC:

251323

AN:

251474

Other (OTH)

AF:

0.982

AC:

23595

AN:

24020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

132

264

395

527

659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

920

1840

2760

3680

4600

<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:

0.936

AC:

142423

AN:

152226

Hom.:

67393

Cov.:

AF XY:

0.938

AC XY:

69834

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.776

AC:

32183

AN:

41490

American (AMR)

AF:

0.977

AC:

14947

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3470

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5186

AN:

5186

South Asian (SAS)

AF:

0.999

AC:

4828

AN:

4832

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.973

AC:

286

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67973

AN:

68008

Other (OTH)

AF:

0.952

AC:

2012

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

395

790

1186

1581

1976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.956

Hom.:

9056

Bravo

AF:

0.926

Asia WGS

AF:

0.986

AC:

3429

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.22

PhyloP100

-0.65

PromoterAI

0.020

Neutral

(source)

Mutation Taster

=100/0

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