Variant chr10-87862193-A-AACC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBP6BS2

The NM_001126049.2(KLLN):c.294_295insGGT(p.Trp98_Cys99insGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000876 in 1,551,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

KLLN
NM_001126049.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.374

Variant links:

Genes affected

KLLN (HGNC:37212): (killin, p53 regulated DNA replication inhibitor) The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by transcription factor p53. [provided by RefSeq, Dec 2012]

KLLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001126049.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 10-87862193-A-AACC is Benign according to our data. Variant chr10-87862193-A-AACC is described in ClinVar as [Likely_benign]. Clinvar id is 3046404.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLLN	NM_001126049.2 link	c.294_295insGGT	p.Trp98_Cys99insGly	conservative_inframe_insertion	Exon 1 of 1	ENST00000445946.5	NP_001119521.1	B2CW77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLLN	ENST00000445946.5 link	c.294_295insGGT	p.Trp98_Cys99insGly	conservative_inframe_insertion	Exon 1 of 1	6	NM_001126049.2	ENSP00000392204.2		B2CW77

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000910

AC:

AN:

153892

Hom.:

AF XY:

0.0000734

AC XY:

AN XY:

81704

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1399318

Hom.:

Cov.:

AF XY:

0.0000377

AC XY:

AN XY:

690164

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000525

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KLLN-related disorder

Benign:1

Apr 06, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over