rs8106384

Positions:

• chr19-16324906-T-C
• chr19-16324906-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KLF2	NM_016270.4	c.-18T>C		5_prime_UTR_variant	1/3	ENST00000248071.6	NP_057354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071	c.-18T>C		5_prime_UTR_variant	1/3	1	NM_016270.4	ENSP00000248071.5
KLF2	ENST00000592003.1	c.-18T>C		5_prime_UTR_variant	1/2	3		ENSP00000465035.1

Frequencies

GnomAD3 genomes AF: 0.999 AC: 151835 AN: 151950 Hom.: 75864 Cov.: 33

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

GnomAD3 exomes AF: 0.999 AC: 214861 AN: 215072 Hom.: 107327 AF XY: 0.999 AC XY: 118740 AN XY: 118856

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 SAS exome AF: 1.00

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.: 33 AF XY: 1.00 AC XY: 714256 AN XY: 714516

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.989

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.999 AC: 151942 AN: 152058 Hom.: 75917 Cov.: 33 AF XY: 0.999 AC XY: 74268 AN XY: 74314

Gnomad4 AFR AF: 1.00

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.999

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	12
DANN	Benign	0.15

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

LitVar

Other links and lift over

dbSNP: rs8106384; hg19: chr19-16435717;