chr19-16324906-T-C

Variant names:

• chr19-16324906-T-C
• rs8106384
• NM_016270.4:c.-18T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016270.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF2	NM_016270.4	MANE Select	c.-18T>C		5_prime_UTR	Exon 1 of 3	NP_057354.1	Q9Y5W3
	KLF2-DT	NR_186323.1		n.-236A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF2	ENST00000248071.6	TSL:1 MANE Select	c.-18T>C		5_prime_UTR	Exon 1 of 3	ENSP00000248071.5	Q9Y5W3
	KLF2	ENST00000592003.1	TSL:3	c.-18T>C		5_prime_UTR	Exon 1 of 2	ENSP00000465035.1	K7EJ60
	KLF2-DT	ENST00000810104.1		n.117A>G		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.999 AC: 214861 AN: 215072 AF XY: 0.999

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.15
PhyloP100		-0.67
PromoterAI		0.098	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8106384; hg19: chr19-16435717;