Genetic Variant KITLG:c.130-12_130-11dupTT (chr12-88532513-C-CAA) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS1

The NM_000899.5(KITLG):c.130-12_130-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,305,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00086 ( 0 hom. )

Consequence

KITLG
NM_000899.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-88532513-C-CAA is Benign according to our data. Variant chr12-88532513-C-CAA is described in ClinVar as [Benign]. Clinvar id is 3628555.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000425 (6/141150) while in subpopulation AFR AF= 0.000157 (6/38306). AF 95% confidence interval is 0.0000681. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5 link	c.130-12_130-11dupTT		intron_variant	Intron 2 of 9	ENST00000644744.1	NP_000890.1	P21583-1A0A024RBC0
KITLG	NM_003994.6 link	c.130-12_130-11dupTT		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_130-10insTT		intron_variant	Intron 2 of 9		NM_000899.5	ENSP00000495951.1		P21583-1

Frequencies

GnomAD3 genomes

AF:

0.0000425

AC:

AN:

141098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000741

AC:

AN:

118740

Hom.:

AF XY:

0.000852

AC XY:

AN XY:

63404

show subpopulations

Gnomad AFR exome

AF:

0.000477

Gnomad AMR exome

AF:

0.00129

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000142

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000574

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000861

AC:

1002

AN:

1163898

Hom.:

Cov.:

AF XY:

0.000854

AC XY:

493

AN XY:

577512

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.000592

Gnomad4 ASJ exome

AF:

0.000360

Gnomad4 EAS exome

AF:

0.000137

Gnomad4 SAS exome

AF:

0.00100

Gnomad4 FIN exome

AF:

0.000511

Gnomad4 NFE exome

AF:

0.000911

Gnomad4 OTH exome

AF:

0.000785

GnomAD4 genome

AF:

0.0000425

AC:

AN:

141150

Hom.:

Cov.:

AF XY:

0.0000439

AC XY:

AN XY:

68410

show subpopulations

Gnomad4 AFR

AF:

0.000157

Gnomad4 AMR

AF:

0.00

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: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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.

12-88532513-CAAAA-CAAAAAA

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