chr10-3780085-G-A

Variant names:

• chr10-3780085-G-A
• rs111743412
• NM_001300.6:c.800+21C>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.800+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,982 control chromosomes in the GnomAD database, including 118 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 0.014 (65 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (53 hom.)
• Consequence: KLF6 NM_001300.6 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.157
• Publications: 0 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 (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2202/152284) while in subpopulation AFR AF = 0.0497 (2065/41556). AF 95% confidence interval is 0.0479. There are 65 homozygotes in GnomAd4. There are 1005 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 2202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF6	NM_001300.6	c.800+21C>T		intron_variant	Intron 3 of 3	ENST00000497571.6	NP_001291.3
KLF6	NM_001160124.2	c.674+21C>T		intron_variant	Intron 3 of 3		NP_001153596.1
KLF6	NM_001160125.2	c.677-495C>T		intron_variant	Intron 2 of 2		NP_001153597.1
KLF6	NR_027653.2	n.841+21C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF6	ENST00000497571.6	c.800+21C>T		intron_variant	Intron 3 of 3	1	NM_001300.6	ENSP00000419923.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2189 AN: 152166 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00393 AC: 988 AN: 251300 AF XY: 0.00294

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00156 AC: 2273 AN: 1461698 Hom.: 53 Cov.: 31 AF XY: 0.00136 AC XY: 988 AN XY: 727162

African (AFR) AF: 0.0508 AC: 1700 AN: 33480

American (AMR) AF: 0.00380 AC: 170 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5766

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1111970

Other (OTH) AF: 0.00406 AC: 245 AN: 60396

GnomAD4 genome AF: 0.0145 AC: 2202 AN: 152284 Hom.: 65 Cov.: 33 AF XY: 0.0135 AC XY: 1005 AN XY: 74468

African (AFR) AF: 0.0497 AC: 2065 AN: 41556

American (AMR) AF: 0.00621 AC: 95 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68016

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00205 Hom.: 1

Bravo AF: 0.0155

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hypotension Other:1

-

Centre for molecular medicine, Karolinska Institutet

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.89
PhyloP100		0.16
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: rs111743412; hg19: chr10-3822277;