NM_001302461.2:c.577+52588C>T

Variant names:

• chr15-31380377-C-T
• rs8033248
• NM_001302461.2:c.577+52588C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302461.2(KLF13):​c.577+52588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,076 control chromosomes in the GnomAD database, including 13,106 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 0.41 (13106 hom., cov: 33)
• Consequence: KLF13 NM_001302461.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 3 publications found

Genes affected

KLF13 (HGNC:13672): (KLF transcription factor 13) KLF13 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

KLF13 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF13	NM_001302461.2	c.577+52588C>T		intron_variant	Intron 1 of 1		NP_001289390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF13	ENST00000558921.1	n.223+52588C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62958 AN: 151956 Hom.: 13105 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.414 AC: 62970 AN: 152076 Hom.: 13106 Cov.: 33 AF XY: 0.416 AC XY: 30903 AN XY: 74338

African (AFR) AF: 0.401 AC: 16638 AN: 41474

American (AMR) AF: 0.445 AC: 6812 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3462

East Asian (EAS) AF: 0.407 AC: 2102 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2267 AN: 4816

European-Finnish (FIN) AF: 0.408 AC: 4309 AN: 10564

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28396 AN: 67980

Other (OTH) AF: 0.383 AC: 809 AN: 2112

Alfa AF: 0.416 Hom.: 8421

Bravo AF: 0.414

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		0.032

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8033248; hg19: chr15-31672580;