chr19-16326424-A-T

Position:

• chr19-16326424-A-T

Variant summary

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

The ENST00000248071.6(KLF2):​c.892+392A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,894 control chromosomes in the GnomAD database, including 1,258 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 0.12 (1258 hom., cov: 31)
• Consequence: KLF2 ENST00000248071.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4	c.892+392A>T		intron_variant		ENST00000248071.6	NP_057354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6	c.892+392A>T		intron_variant		1	NM_016270.4	ENSP00000248071	P1
KLF2	ENST00000592003.1	c.76-432A>T		intron_variant		3		ENSP00000465035

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18614 AN: 151776 Hom.: 1256 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18620 AN: 151894 Hom.: 1258 Cov.: 31 AF XY: 0.119 AC XY: 8847 AN XY: 74234

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.0144

Gnomad4 SAS AF: 0.0960

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.142

Alfa AF: 0.0664 Hom.: 68

Bravo AF: 0.127

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7258799; hg19: chr19-16437235;