12-88515401-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000899.5(KITLG):c.604+133T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 616,942 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.013 (55 hom.)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 12-88515401-A-C is Benign according to our data. Variant chr12-88515401-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1194205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1557/151954) while in subpopulation NFE AF= 0.0165 (1120/67754). AF 95% confidence interval is 0.0157. There are 12 homozygotes in gnomad4. There are 714 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KITLG	NM_000899.5	c.604+133T>G		intron_variant		ENST00000644744.1
KITLG	NM_003994.6	c.520+933T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KITLG	ENST00000644744.1	c.604+133T>G		intron_variant			NM_000899.5	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1556 AN: 151836 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00381

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00718

GnomAD4 exome AF: 0.0126 AC: 5837 AN: 464988 Hom.: 55 AF XY: 0.0125 AC XY: 3122 AN XY: 248918

Gnomad4 AFR exome AF: 0.00382

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.0110

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.00744

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0102 AC: 1557 AN: 151954 Hom.: 12 Cov.: 32 AF XY: 0.00961 AC XY: 714 AN XY: 74312

Gnomad4 AFR AF: 0.00335

Gnomad4 AMR AF: 0.00381

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.0129 Hom.: 0

Bravo AF: 0.00915

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	1.6
Dann	Benign	0.73

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: rs190711063; hg19: chr12-88909178;