Variant rs151218732 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022148.4(CRLF2):c.730G>C(p.Val244Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,648 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 1 hem., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. 3 hem. )

Consequence

CRLF2
NM_022148.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.856

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:

CRLF2 (HGNC:):

CRLF2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17448077).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRLF2	NM_022148.4 linkuse as main transcript	c.730G>C	p.Val244Leu	missense_variant	6/8	ENST00000400841.8	NP_071431.2	Q9HC73-1D0E2W4
CRLF2	NM_001012288.3 linkuse as main transcript	c.394G>C	p.Val132Leu	missense_variant	5/7		NP_001012288.2	Q9HC73-3
CRLF2	XM_011546181.3 linkuse as main transcript	c.727G>C	p.Val243Leu	missense_variant	6/8		XP_011544483.1
CRLF2	NR_110830.2 linkuse as main transcript	n.924G>C		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRLF2	ENST00000400841.8 linkuse as main transcript	c.730G>C	p.Val244Leu	missense_variant	6/8	1	NM_022148.4	ENSP00000383641.3	Q9HC73-1
CRLF2	ENST00000381567.8 linkuse as main transcript	c.394G>C	p.Val132Leu	missense_variant	5/7	1		ENSP00000370979.4	Q9HC73-3
CRLF2	ENST00000467626.6 linkuse as main transcript	n.*210G>C		non_coding_transcript_exon_variant	6/8	5		ENSP00000485269.1	A0A0C4DH06
CRLF2	ENST00000467626.6 linkuse as main transcript	n.*210G>C		3_prime_UTR_variant	6/8	5		ENSP00000485269.1	A0A0C4DH06

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151648

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74012

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461000

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151648

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74012

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Benign

0.0090

DEOGEN2

Benign

0.023

T;T;.

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.37

T;.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.29

.;N;.

REVEL

Benign

0.24

Sift

Pathogenic

0.0

.;D;.

Sift4G

Benign

0.072

T;T;T

Polyphen

0.22

B;B;.

Vest4

0.31

MutPred

0.48

Loss of catalytic residue at V244 (P = 0.0084);Loss of catalytic residue at V244 (P = 0.0084);.;

MVP

0.74

MPC

0.060

ClinPred

0.038

GERP RS

-3.0

Varity_R

0.039

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over