10-3782241-C-T

Variant names:

• chr10-3782241-C-T
• rs3750861
• NM_001300.6:c.103-27G>A

Variant summary

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

The NM_001300.6(KLF6):​c.103-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 1,577,916 control chromosomes in the GnomAD database, including 5,020 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.066 (408 hom., cov: 33)
  • Exomes 𝑓: 0.078 (4612 hom.)
• Consequence: KLF6 NM_001300.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 51 publications found

Genes affected

KLF6 (HGNC:2235): (KLF transcription factor 6) This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis. [provided by RefSeq, May 2009]

ACMG classification

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.103-27G>A		intron	N/A	NP_001291.3
	KLF6	NM_001160124.2		c.103-27G>A		intron	N/A	NP_001153596.1
	KLF6	NM_001160125.2		c.103-27G>A		intron	N/A	NP_001153597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.103-27G>A		intron	N/A	ENSP00000419923.1
	KLF6	ENST00000469435.1	TSL:1	c.103-27G>A		intron	N/A	ENSP00000419079.1
	KLF6	ENST00000542957.1	TSL:5	c.103-27G>A		intron	N/A	ENSP00000445301.1

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10109 AN: 152088 Hom.: 401 Cov.: 33

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0867

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0670

GnomAD2 exomes AF: 0.0820 AC: 19446 AN: 237078 AF XY: 0.0814

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.0480

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0766

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.0781 AC: 111310 AN: 1425710 Hom.: 4612 Cov.: 26 AF XY: 0.0778 AC XY: 55314 AN XY: 711112

African (AFR) AF: 0.0311 AC: 1027 AN: 32996

American (AMR) AF: 0.126 AC: 5633 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.0604 AC: 1568 AN: 25980

East Asian (EAS) AF: 0.0425 AC: 1683 AN: 39582

South Asian (SAS) AF: 0.0861 AC: 7384 AN: 85730

European-Finnish (FIN) AF: 0.115 AC: 4680 AN: 40584

Middle Eastern (MID) AF: 0.0778 AC: 447 AN: 5742

European-Non Finnish (NFE) AF: 0.0775 AC: 84528 AN: 1090988

Other (OTH) AF: 0.0733 AC: 4360 AN: 59510

GnomAD4 genome AF: 0.0665 AC: 10121 AN: 152206 Hom.: 408 Cov.: 33 AF XY: 0.0674 AC XY: 5018 AN XY: 74418

African (AFR) AF: 0.0328 AC: 1362 AN: 41514

American (AMR) AF: 0.0874 AC: 1337 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3470

East Asian (EAS) AF: 0.0442 AC: 229 AN: 5184

South Asian (SAS) AF: 0.0896 AC: 432 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5101 AN: 68012

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0701 Hom.: 1291

Bravo AF: 0.0654

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.4
DANN	Benign	0.96
PhyloP100		-1.1
BranchPoint Hunter		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3750861; hg19: chr10-3824433; COSMIC: COSV51495429;