rs186624120

Variant names:

• chr10-3781580-G-A
• rs186624120
• ENST00000469435.1:c.737C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001300.6(KLF6):​c.676+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,599,390 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0049 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (14 hom.)
• Consequence: KLF6 NM_001300.6 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.96
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004200399).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00491 (748/152356) while in subpopulation AFR AF = 0.0171 (711/41594). AF 95% confidence interval is 0.0161. There are 4 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6	c.676+61C>T		intron_variant	Intron 2 of 3	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2	c.550+187C>T		intron_variant	Intron 2 of 3		NP_001153596.1
KLF6	NM_001160125.2	c.676+61C>T		intron_variant	Intron 2 of 2		NP_001153597.1
KLF6	NR_027653.2	n.717+215C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6	c.676+61C>T		intron_variant	Intron 2 of 3	1	NM_001300.6	ENSP00000419923.1

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 747 AN: 152238 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00106 AC: 230 AN: 216630 AF XY: 0.000827

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000321

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000469 AC: 679 AN: 1447034 Hom.: 14 Cov.: 32 AF XY: 0.000383 AC XY: 275 AN XY: 718872

African (AFR) AF: 0.0170 AC: 561 AN: 33068

American (AMR) AF: 0.000644 AC: 27 AN: 41922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 38684

South Asian (SAS) AF: 0.00 AC: 0 AN: 84786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52192

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5750

European-Non Finnish (NFE) AF: 0.0000145 AC: 16 AN: 1104954

Other (OTH) AF: 0.00122 AC: 73 AN: 59840

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152356 Hom.: 4 Cov.: 33 AF XY: 0.00491 AC XY: 366 AN XY: 74508

African (AFR) AF: 0.0171 AC: 711 AN: 41594

American (AMR) AF: 0.00189 AC: 29 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00275 Hom.: 1

Bravo AF: 0.00526

ExAC AF: 0.00143 AC: 171

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Uncertain	1.0
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.0
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.042
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.12
MVP		0.44
ClinPred		0.015	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

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: rs186624120; hg19: chr10-3823772;