10-3782086-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001300.6(KLF6):c.231C>T(p.Ser77=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,614,020 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (64 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (49 hom.)
• Consequence: KLF6 NM_001300.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-3782086-G-A is Benign according to our data. Variant chr10-3782086-G-A is described in ClinVar as [Benign]. Clinvar id is 717974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.11 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2191/152198) while in subpopulation AFR AF= 0.0494 (2052/41504). AF 95% confidence interval is 0.0477. There are 64 homozygotes in gnomad4. There are 998 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.231C>T	p.Ser77=	synonymous_variant	2/4	ENST00000497571.6
KLF6	NM_001160124.2	c.231C>T	p.Ser77=	synonymous_variant	2/4
KLF6	NM_001160125.2	c.231C>T	p.Ser77=	synonymous_variant	2/3
KLF6	NR_027653.2	n.426C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.231C>T	p.Ser77=	synonymous_variant	2/4	1	NM_001300.6	P1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2181 AN: 152080 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

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

GnomAD3 exomes AF: 0.00393 AC: 989 AN: 251482 Hom.: 18 AF XY: 0.00294 AC XY: 400 AN XY: 135916

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00152 AC: 2226 AN: 1461822 Hom.: 49 Cov.: 32 AF XY: 0.00133 AC XY: 968 AN XY: 727222

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.0144 AC: 2191 AN: 152198 Hom.: 64 Cov.: 33 AF XY: 0.0134 AC XY: 998 AN XY: 74416

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00542 Hom.: 8

Bravo AF: 0.0155

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.55
Dann	Benign	0.82

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: rs35835052; hg19: chr10-3824278;