4-38682580-C-T

Position:

• chr4-38682580-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016531.6(KLF3):​c.57+1898C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,158 control chromosomes in the GnomAD database, including 57,394 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 0.86 (57394 hom., cov: 31)
• Consequence: KLF3 NM_016531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

Genes affected

KLF3 (HGNC:16516): (KLF transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF3	NM_016531.6	c.57+1898C>T		intron_variant		ENST00000261438.10
KLF3	XM_047415764.1	c.-243+1898C>T		intron_variant
KLF3	XR_925142.2	n.359+1898C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF3	ENST00000261438.10	c.57+1898C>T		intron_variant		1	NM_016531.6	P1
KLF3	ENST00000514033.1	c.57+1898C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131334 AN: 152040 Hom.: 57331 Cov.: 31

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.864 AC: 131455 AN: 152158 Hom.: 57394 Cov.: 31 AF XY: 0.861 AC XY: 64013 AN XY: 74386

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.812

Alfa AF: 0.853 Hom.: 6898

Bravo AF: 0.864

Asia WGS AF: 0.798 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs6531656; hg19: chr4-38684201;