rs12462380

Positions:

• chr19-16326237-A-G

Variant summary

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

The ENST00000248071.6(KLF2):​c.892+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.49 (15703 hom., cov: 20)
• Consequence: KLF2 ENST00000248071.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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 = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4	c.892+205A>G		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+205A>G		intron_variant		1	NM_016270.4	ENSP00000248071	P1
KLF2	ENST00000592003.1	c.76-619A>G		intron_variant		3		ENSP00000465035

Frequencies

GnomAD3 genomes AF: 0.488 AC: 66696 AN: 136626 Hom.: 15671 Cov.: 20

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.488 AC: 66775 AN: 136714 Hom.: 15703 Cov.: 20 AF XY: 0.495 AC XY: 32559 AN XY: 65786

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.464

Alfa AF: 0.433 Hom.: 12958

Bravo AF: 0.471

Asia WGS AF: 0.476 AC: 1655 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12462380; hg19: chr19-16437048;