rs41283112

Positions:

chr12-88507114-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000899.5(KITLG):c.628G>T(p.Asp210Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,446 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 32)

Exomes 𝑓: 0.016 ( 214 hom. )

Consequence

KITLG
NM_000899.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.05

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:

KITLG (HGNC:):

KITLG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009672701).

BP6

Variant 12-88507114-C-A is Benign according to our data. Variant chr12-88507114-C-A is described in ClinVar as [Benign]. Clinvar id is 508156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.01 (1524/152272) while in subpopulation NFE AF= 0.0163 (1109/68024). AF 95% confidence interval is 0.0155. There are 12 homozygotes in gnomad4. There are 691 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5 linkuse as main transcript	c.628G>T	p.Asp210Tyr	missense_variant	7/10	ENST00000644744.1	NP_000890.1	P21583-1A0A024RBC0
KITLG	NM_003994.6 linkuse as main transcript	c.544G>T	p.Asp182Tyr	missense_variant	6/9		NP_003985.2	P21583-2A0A024RBF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1 linkuse as main transcript	c.628G>T	p.Asp210Tyr	missense_variant	7/10		NM_000899.5	ENSP00000495951.1		P21583-1

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1523

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00336

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.0101

AC:

2534

AN:

250846

Hom.:

AF XY:

0.00991

AC XY:

1344

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00914

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00516

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.00998

GnomAD4 exome

AF:

0.0155

AC:

22687

AN:

1460174

Hom.:

214

Cov.:

AF XY:

0.0150

AC XY:

10920

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00900

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00520

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0131

GnomAD4 genome

AF:

0.0100

AC:

1524

AN:

152272

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

691

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00335

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.00893

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0160

AC:

138

ExAC

AF:

0.0105

AC:

1272

Asia WGS

AF:

0.00173

AC:

AN:

3474

EpiCase

AF:

0.0149

EpiControl

AF:

0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 23, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Asp210Tyr in exon 7 of KITLG: This variant is not expected to have clinical si gnificance because it has been identified in 1.55% (1029/66452) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs41283112). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;.;D

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.75

.;T;T

MetaRNN

Benign

0.0097

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.9

.;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0090

.;D;D

Sift4G

Uncertain

0.0070

.;D;D

Polyphen

1.0

D;D;D

Vest4

0.58, 0.62

MPC

0.84

ClinPred

0.011

GERP RS

2.8

Varity_R

0.16

gMVP

0.41

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.

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