Genetic Variant NM_001199805.1: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC4-KLRK1	NM_001199805.1 link	c.-488+75C>T		intron_variant	Intron 1 of 12		NP_001186734.1	P26718-1A0A024RAP8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
KLRC4-KLRK1	ENST00000543812.5 link	n.-63+75C>T	intron_variant	Intron 1 of 12	2	ENSP00000457500.1	H3BU71
KLRC4-KLRK1	ENST00000585507.5 link	n.-63+75C>T	intron_variant	Intron 1 of 10	5	ENSP00000465434.1	H3BU71
KLRC4-KLRK1	ENST00000588263.5 link	n.-153+75C>T	intron_variant	Intron 1 of 10	5	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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over