chr15-31332837-T-C

Variant names:

• chr15-31332837-T-C
• rs4779516
• NM_015995.4:c.577+5048T>C

Variant summary

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

The NM_015995.4(KLF13):​c.577+5048T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,978 control chromosomes in the GnomAD database, including 13,578 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 (13578 hom., cov: 32)
• Consequence: KLF13 NM_015995.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015995.4. 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
	KLF13	NM_015995.4	MANE Select	c.577+5048T>C		intron	N/A	NP_057079.2
	KLF13	NM_001302461.2		c.577+5048T>C		intron	N/A	NP_001289390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF13	ENST00000307145.4	TSL:1 MANE Select	c.577+5048T>C		intron	N/A	ENSP00000302456.3	Q9Y2Y9
	KLF13	ENST00000870899.1		c.163+5462T>C		intron	N/A	ENSP00000540958.1
	KLF13	ENST00000558921.1	TSL:3	n.223+5048T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61528 AN: 151860 Hom.: 13568 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.405 AC: 61562 AN: 151978 Hom.: 13578 Cov.: 32 AF XY: 0.413 AC XY: 30691 AN XY: 74282

African (AFR) AF: 0.232 AC: 9627 AN: 41452

American (AMR) AF: 0.416 AC: 6356 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.588 AC: 3031 AN: 5156

South Asian (SAS) AF: 0.602 AC: 2907 AN: 4828

European-Finnish (FIN) AF: 0.508 AC: 5360 AN: 10560

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31472 AN: 67948

Other (OTH) AF: 0.398 AC: 839 AN: 2106

Alfa AF: 0.445 Hom.: 3202

Bravo AF: 0.389

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.56
PhyloP100		0.38
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: rs4779516; hg19: chr15-31625040;