12-88532513-CAAAA-CAAA

Position:

• chr12-88532513-CAAAA-CAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000899.5(KITLG):​c.130-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,162,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 30)
  • Exomes 𝑓: 0.034 (0 hom.)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.318

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-88532513-CA-C is Benign according to our data. Variant chr12-88532513-CA-C is described in ClinVar as [Benign]. Clinvar id is 1272999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5	c.130-11delT		intron_variant		ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.130-11delT		intron_variant			NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.130-11delT		intron_variant			NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.000397 AC: 56 AN: 140946 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000711

Gnomad ASJ AF: 0.000603

Gnomad EAS AF: 0.000206

Gnomad SAS AF: 0.000222

Gnomad FIN AF: 0.00129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000341

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0513 AC: 6095 AN: 118740 Hom.: 0 AF XY: 0.0500 AC XY: 3173 AN XY: 63404

Gnomad AFR exome AF: 0.0347

Gnomad AMR exome AF: 0.0901

Gnomad ASJ exome AF: 0.0734

Gnomad EAS exome AF: 0.0726

Gnomad SAS exome AF: 0.0575

Gnomad FIN exome AF: 0.0535

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0687

GnomAD4 exome AF: 0.0335 AC: 34257 AN: 1021590 Hom.: 0 Cov.: 23 AF XY: 0.0334 AC XY: 16757 AN XY: 502458

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.0430

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.0448

Gnomad4 FIN exome AF: 0.0412

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.000397 AC: 56 AN: 140992 Hom.: 0 Cov.: 30 AF XY: 0.000498 AC XY: 34 AN XY: 68318

Gnomad4 AFR AF: 0.000235

Gnomad4 AMR AF: 0.000711

Gnomad4 ASJ AF: 0.000603

Gnomad4 EAS AF: 0.000207

Gnomad4 SAS AF: 0.000223

Gnomad4 FIN AF: 0.00129

Gnomad4 NFE AF: 0.000342

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 24, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2019	- -

Computational scores

Source: dbNSFP v4.3

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: rs11428619; hg19: chr12-88926290;