19-16325042-C-T

Variant names:

• chr19-16325042-C-T
• rs7248864
• NM_016270.4:c.75+44C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016270.4(KLF2):​c.75+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,495,912 control chromosomes in the GnomAD database, including 11,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1532 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10008 hom.)
• Consequence: KLF2 NM_016270.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-16325042-C-T is Benign according to our data. Variant chr19-16325042-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 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.75+44C>T		intron	N/A	NP_057354.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF2	ENST00000248071.6	TSL:1 MANE Select	c.75+44C>T		intron	N/A	ENSP00000248071.5
	KLF2	ENST00000592003.1	TSL:3	c.75+44C>T		intron	N/A	ENSP00000465035.1
	KLF2-DT	ENST00000810104.1		n.-20G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20583 AN: 151980 Hom.: 1529 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.152 AC: 18894 AN: 124374 AF XY: 0.147

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0789

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.118 AC: 158115 AN: 1343822 Hom.: 10008 Cov.: 24 AF XY: 0.117 AC XY: 77866 AN XY: 664626

African (AFR) AF: 0.191 AC: 5533 AN: 28956

American (AMR) AF: 0.211 AC: 6887 AN: 32614

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 2066 AN: 22678

East Asian (EAS) AF: 0.0635 AC: 2154 AN: 33922

South Asian (SAS) AF: 0.130 AC: 9885 AN: 75936

European-Finnish (FIN) AF: 0.183 AC: 8096 AN: 44192

Middle Eastern (MID) AF: 0.109 AC: 477 AN: 4382

European-Non Finnish (NFE) AF: 0.111 AC: 116484 AN: 1045588

Other (OTH) AF: 0.118 AC: 6533 AN: 55554

GnomAD4 genome AF: 0.135 AC: 20596 AN: 152090 Hom.: 1532 Cov.: 33 AF XY: 0.137 AC XY: 10158 AN XY: 74370

African (AFR) AF: 0.173 AC: 7177 AN: 41528

American (AMR) AF: 0.136 AC: 2081 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0906 AC: 314 AN: 3466

East Asian (EAS) AF: 0.0753 AC: 389 AN: 5168

South Asian (SAS) AF: 0.125 AC: 602 AN: 4818

European-Finnish (FIN) AF: 0.189 AC: 2005 AN: 10588

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.111 AC: 7533 AN: 67926

Other (OTH) AF: 0.111 AC: 234 AN: 2108

Alfa AF: 0.110 Hom.: 1133

Bravo AF: 0.136

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		1.3
PromoterAI		-0.00020	Neutral
Mutation Taster		=100/0	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: rs7248864; hg19: chr19-16435853; COSMIC: COSV50179675; COSMIC: COSV50179675;