Variant rs200254974 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022148.4(CRLF2):c.637G>A(p.Glu213Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000356 in 1,613,642 control chromosomes in the GnomAD database, including 4 homozygotes. There are 371 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 20 hem., cov: 30)

Exomes 𝑓: 0.00037 ( 4 hom. 351 hem. )

Consequence

CRLF2
NM_022148.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

CRLF2 (HGNC:14281): (cytokine receptor like factor 2) This gene encodes a member of the type I cytokine receptor family. The encoded protein is a receptor for thymic stromal lymphopoietin (TSLP). Together with the interleukin 7 receptor (IL7R), the encoded protein and TSLP activate STAT3, STAT5, and JAK2 pathways, which control processes such as cell proliferation and development of the hematopoietic system. Rearrangement of this gene with immunoglobulin heavy chain gene (IGH) on chromosome 14, or with P2Y purinoceptor 8 gene (P2RY8) on the same X or Y chromosomes is associated with B-progenitor acute lymphoblastic leukemia (ALL) and Down syndrome ALL. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

CRLF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009222776).

BS2

High Hemizygotes in GnomAd at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRLF2	NM_022148.4 linkuse as main transcript	c.637G>A	p.Glu213Lys	missense_variant	5/8	ENST00000400841.8
CRLF2	NM_001012288.3 linkuse as main transcript	c.301G>A	p.Glu101Lys	missense_variant	4/7
CRLF2	XM_011546181.3 linkuse as main transcript	c.634G>A	p.Glu212Lys	missense_variant	5/8
CRLF2	NR_110830.2 linkuse as main transcript	n.840+230G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF2	ENST00000400841.8 linkuse as main transcript	c.637G>A	p.Glu213Lys	missense_variant	5/8	1	NM_022148.4	P1	Q9HC73-1
CRLF2	ENST00000381567.8 linkuse as main transcript	c.301G>A	p.Glu101Lys	missense_variant	4/7	1			Q9HC73-3
CRLF2	ENST00000467626.6 linkuse as main transcript	c.*126+230G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74270

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000643

AC:

160

AN:

248818

Hom.:

AF XY:

0.000837

AC XY:

113

AN XY:

134958

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000369

AC:

540

AN:

1461454

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

351

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000157

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000230

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000471

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.000570

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

Cadd

Benign

0.32

Dann

Benign

0.30

DEOGEN2

Benign

0.021

T;T;.

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.50

T;.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

Sift4G

Benign

0.55

T;T;T

Polyphen

0.033

B;B;.

Vest4

0.13

MVP

0.81

MPC

0.079

ClinPred

0.0071

GERP RS

-3.8

Varity_R

0.076

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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