Genetic Variant KITLG:c.130-11dupT (chr12-88532513-C-CA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000899.5(KITLG):c.130-11dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,239,402 control chromosomes in the GnomAD database, including 2,098 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 601 hom., cov: 30)

Exomes 𝑓: 0.14 ( 1497 hom. )

Consequence

KITLG
NM_000899.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.318

Variant links:

Genes affected

KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KITLG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-88532513-C-CA is Benign according to our data. Variant chr12-88532513-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 517646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5 link	c.130-11dupT		intron_variant	Intron 2 of 9	ENST00000644744.1	NP_000890.1	P21583-1A0A024RBC0
KITLG	NM_003994.6 link	c.130-11dupT		intron_variant	Intron 2 of 8		NP_003985.2	P21583-2A0A024RBF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1 link	c.130-11_130-10insT		intron_variant	Intron 2 of 9		NM_000899.5	ENSP00000495951.1		P21583-1

Frequencies

GnomAD3 genomes

AF:

0.0944

AC:

13312

AN:

141008

Hom.:

600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.0752

Gnomad AMR

AF:

0.0835

Gnomad ASJ

AF:

0.0663

Gnomad EAS

AF:

0.0115

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0974

Gnomad MID

AF:

0.0690

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.165

AC:

19607

AN:

118740

Hom.:

178

AF XY:

0.172

AC XY:

10933

AN XY:

63404

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0296

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.136

AC:

148939

AN:

1098342

Hom.:

1497

Cov.:

AF XY:

0.137

AC XY:

74407

AN XY:

543938

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0931

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0545

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.132

GnomAD4 genome

AF:

0.0944

AC:

13315

AN:

141060

Hom.:

601

Cov.:

AF XY:

0.0929

AC XY:

6353

AN XY:

68370

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.0834

Gnomad4 ASJ

AF:

0.0663

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0974

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.108

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 13, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is present in 15% (21777/141927) of all chromosomes in the Genome A ggregation Database (gnomAD, http://gnomad.broadinstitute.org, rs11428619) and i s therefore benign. -

Hyperpigmentation with or without hypopigmentation, familial progressive;C2674081:SKIN/HAIR/EYE PIGMENTATION 7, DARK/LIGHT SKIN;C4225241:Autosomal dominant nonsyndromic hearing loss 69

Benign:1

Sep 27, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

12-88532513-CAAAA-CAAAAA

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