dbSNP rs17549004: KLRC4-KLRK1:c.-488+75C>T (chr12-10410024-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001199805.1(KLRC4-KLRK1):c.-488+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,342 control chromosomes in the GnomAD database, including 1,683 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 0.13 ( 1680 hom., cov: 33)

Exomes 𝑓: 0.091 ( 3 hom. )

Consequence

KLRC4-KLRK1
NM_001199805.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00400

Publications

4 publications found

Variant links:

Genes affected

KLRC4-KLRK1 (HGNC:48357): (KLRC4-KLRK1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring KLRC4 (killer cell lectin-like receptor subfamily C, member 4) and KLRK1 (killer cell lectin-like receptor subfamily K, member 1) genes on chromosome 12. The read-through transcript includes an alternate 5' exon and lacks a significant portion of the KLRC4 coding sequence, including the start codon, and it thus encodes the KLRK1 protein. [provided by RefSeq, Dec 2010]

KLRC4-KLRK1 links:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199805.1. 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
	KLRC4-KLRK1	NM_001199805.1		c.-488+75C>T		intron	N/A	NP_001186734.1	P26718-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLRC4-KLRK1	ENST00000543812.5	TSL:2	n.-63+75C>T	intron	N/A	ENSP00000457500.1	H3BU71
KLRC4-KLRK1	ENST00000585507.5	TSL:5	n.-63+75C>T	intron	N/A	ENSP00000465434.1	H3BU71
KLRC4-KLRK1	ENST00000588263.5	TSL:5	n.-153+75C>T	intron	N/A	ENSP00000468074.1	H3BU71

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20058

AN:

151874

Hom.:

1682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.0914

AC:

AN:

350

Hom.:

AF XY:

0.0981

AC XY:

AN XY:

214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.104

AC:

AN:

280

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.132

AC:

20048

AN:

151992

Hom.:

1680

Cov.:

AF XY:

0.132

AC XY:

9774

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0371

AC:

1538

AN:

41494

American (AMR)

AF:

0.103

AC:

1565

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3468

East Asian (EAS)

AF:

0.218

AC:

1128

AN:

5166

South Asian (SAS)

AF:

0.109

AC:

524

AN:

4818

European-Finnish (FIN)

AF:

0.176

AC:

1857

AN:

10538

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12247

AN:

67940

Other (OTH)

AF:

0.141

AC:

297

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

865

1729

2594

3458

4323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.127

Hom.:

448

Bravo

AF:

0.126

Asia WGS

AF:

0.142

AC:

487

AN:

3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.7

(source)

DANN

Benign

0.53

PhyloP100

-0.0040

PromoterAI

0.022

Neutral

(source)

Splicing

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