NM_016531.6:c.-40+890C>T

Variant names:

• chr4-38665351-C-T
• rs9522
• NM_016531.6:c.-40+890C>T

Variant summary

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

The NM_016531.6(KLF3):​c.-40+890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,904 control chromosomes in the GnomAD database, including 14,076 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 (14076 hom., cov: 31)
• Consequence: KLF3 NM_016531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016531.6. 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
	KLF3	NM_016531.6	MANE Select	c.-40+890C>T		intron	N/A	NP_057615.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF3	ENST00000261438.10	TSL:1 MANE Select	c.-40+890C>T		intron	N/A	ENSP00000261438.5	P57682-1
	KLF3	ENST00000514033.1	TSL:1	c.-40+890C>T		intron	N/A	ENSP00000421252.1	P57682-2
	KLF3	ENST00000928716.1		c.-40+890C>T		intron	N/A	ENSP00000598775.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64194 AN: 151784 Hom.: 14056 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.423 AC: 64262 AN: 151904 Hom.: 14076 Cov.: 31 AF XY: 0.420 AC XY: 31183 AN XY: 74234

African (AFR) AF: 0.410 AC: 16983 AN: 41428

American (AMR) AF: 0.427 AC: 6523 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3466

East Asian (EAS) AF: 0.151 AC: 777 AN: 5154

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4822

European-Finnish (FIN) AF: 0.501 AC: 5273 AN: 10526

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30760 AN: 67916

Other (OTH) AF: 0.395 AC: 832 AN: 2106

Alfa AF: 0.438 Hom.: 50237

Bravo AF: 0.420

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.024
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: rs9522; hg19: chr4-38666972;