Genetic Variant NM_016270.4:c.-18T>C (chr19-16324906-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016270.4(KLF2):c.-18T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,588,994 control chromosomes in the GnomAD database, including 793,831 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 1.0 ( 75917 hom., cov: 33)

Exomes 𝑓: 1.0 ( 717914 hom. )

Consequence

KLF2
NM_016270.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.665

Publications

7 publications found

Variant links:

Genes affected

KLF2 (HGNC:6347): (KLF transcription factor 2) This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is expressed early in mammalian development and is found in many different cell types. The protein acts to bind the CACCC box found in the promoter of target genes to activate their transcription. It plays a role in many processes during development and disease including adipogenesis, embryonic erythropoiesis, epithelial integrity, inflammation and t-cell viability. [provided by RefSeq, Mar 2017]

KLF2 links:

KLF2-DT (HGNC:55304): (KLF2 divergent transcript)

KLF2-DT 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF2	NM_016270.4 link	c.-18T>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000248071.6	NP_057354.1	Q9Y5W3
KLF2-DT	NR_186323.1 link	n.-236A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6 link	c.-18T>C		5_prime_UTR_variant	Exon 1 of 3	1	NM_016270.4	ENSP00000248071.5		Q9Y5W3

Frequencies

GnomAD3 genomes

AF:

0.999

AC:

151835

AN:

151950

Hom.:

75864

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD2 exomes

AF:

0.999

AC:

214861

AN:

215072

AF XY:

0.999

show subpopulations

Gnomad AFR exome

AF:

1.00

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.987

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

1.00

AC:

1436370

AN:

1436936

Hom.:

717914

Cov.:

AF XY:

1.00

AC XY:

714256

AN XY:

714516

show subpopulations

African (AFR)

AF:

1.00

AC:

30533

AN:

30536

American (AMR)

AF:

1.00

AC:

43240

AN:

43244

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

25170

AN:

25170

East Asian (EAS)

AF:

0.989

AC:

36898

AN:

37298

South Asian (SAS)

AF:

1.00

AC:

83480

AN:

83482

European-Finnish (FIN)

AF:

1.00

AC:

51117

AN:

51118

Middle Eastern (MID)

AF:

1.00

AC:

5586

AN:

5586

European-Non Finnish (NFE)

AF:

1.00

AC:

1101300

AN:

1101314

Other (OTH)

AF:

0.998

AC:

59046

AN:

59188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21518

43036

64554

86072

107590

<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:

0.999

AC:

151942

AN:

152058

Hom.:

75917

Cov.:

AF XY:

0.999

AC XY:

74268

AN XY:

74314

show subpopulations

African (AFR)

AF:

1.00

AC:

41535

AN:

41548

American (AMR)

AF:

0.998

AC:

15263

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

0.986

AC:

5032

AN:

5104

South Asian (SAS)

AF:

1.00

AC:

4830

AN:

4830

European-Finnish (FIN)

AF:

1.00

AC:

10540

AN:

10540

Middle Eastern (MID)

AF:

1.00

AC:

292

AN:

292

European-Non Finnish (NFE)

AF:

1.00

AC:

67957

AN:

67958

Other (OTH)

AF:

0.999

AC:

2111

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

1.00

Hom.:

12595

Bravo

AF:

0.999

Asia WGS

AF:

0.992

AC:

3435

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.15

PhyloP100

-0.67

PromoterAI

0.098

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over