chr15-31354066-G-A

Variant names:

• chr15-31354066-G-A
• rs12592176
• NM_015995.4:c.578-17944G>A

Variant summary

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

The NM_015995.4(KLF13):​c.578-17944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,132 control chromosomes in the GnomAD database, including 14,627 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 0.42 (14627 hom., cov: 33)
• Consequence: KLF13 NM_015995.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 1 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

ENSG00000298136 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF13	NM_015995.4	c.578-17944G>A		intron_variant	Intron 1 of 1	ENST00000307145.4	NP_057079.2
KLF13	NM_001302461.2	c.577+26277G>A		intron_variant	Intron 1 of 1		NP_001289390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF13	ENST00000307145.4	c.578-17944G>A		intron_variant	Intron 1 of 1	1	NM_015995.4	ENSP00000302456.3
KLF13	ENST00000560473.1	c.13+14079G>A		intron_variant	Intron 1 of 1	3		ENSP00000452609.1
KLF13	ENST00000558921.1	n.223+26277G>A		intron_variant	Intron 1 of 1	3
ENSG00000298136	ENST00000753213.1	n.263-339G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64529 AN: 152016 Hom.: 14628 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.424 AC: 64539 AN: 152132 Hom.: 14627 Cov.: 33 AF XY: 0.423 AC XY: 31430 AN XY: 74358

African (AFR) AF: 0.253 AC: 10506 AN: 41534

American (AMR) AF: 0.398 AC: 6085 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2907 AN: 5166

South Asian (SAS) AF: 0.461 AC: 2219 AN: 4814

European-Finnish (FIN) AF: 0.477 AC: 5038 AN: 10572

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34560 AN: 67966

Other (OTH) AF: 0.433 AC: 913 AN: 2110

Alfa AF: 0.450 Hom.: 2086

Bravo AF: 0.413

Asia WGS AF: 0.452 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.38
PhyloP100		-2.2
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: rs12592176; hg19: chr15-31646269;