Variant X-1196817-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022148.4(CRLF2):c.730G>A(p.Val244Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,612,362 control chromosomes in the GnomAD database, including 3,672 homozygotes. There are 50,786 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/13 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 0.073 ( 459 hom., 5396 hem., cov: 31)

Exomes 𝑓: 0.063 ( 3213 hom. 45390 hem. )

Consequence

CRLF2
NM_022148.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023950338).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CRLF2	NM_022148.4 linkuse as main transcript	c.730G>A	p.Val244Met	missense_variant	6/8	ENST00000400841.8
CRLF2	NM_001012288.3 linkuse as main transcript	c.394G>A	p.Val132Met	missense_variant	5/7
CRLF2	XM_011546181.3 linkuse as main transcript	c.727G>A	p.Val243Met	missense_variant	6/8
CRLF2	NR_110830.2 linkuse as main transcript	n.924G>A		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRLF2	ENST00000400841.8 linkuse as main transcript	c.730G>A	p.Val244Met	missense_variant	6/8	1	NM_022148.4	P1	Q9HC73-1
CRLF2	ENST00000381567.8 linkuse as main transcript	c.394G>A	p.Val132Met	missense_variant	5/7	1			Q9HC73-3
CRLF2	ENST00000467626.6 linkuse as main transcript	c.*210G>A		3_prime_UTR_variant, NMD_transcript_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.0726

AC:

11000

AN:

151616

Hom.:

458

Cov.:

AF XY:

0.0728

AC XY:

5390

AN XY:

73992

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0554

Gnomad ASJ

AF:

0.0603

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.0471

Gnomad FIN

AF:

0.0930

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0718

GnomAD4 exome

AF:

0.0627

AC:

91610

AN:

1460628

Hom.:

3213

Cov.:

AF XY:

0.0625

AC XY:

45390

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.0948

Gnomad4 AMR exome

AF:

0.0357

Gnomad4 ASJ exome

AF:

0.0573

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0501

Gnomad4 FIN exome

AF:

0.0877

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0628

GnomAD4 genome

AF:

0.0726

AC:

11010

AN:

151734

Hom.:

459

Cov.:

AF XY:

0.0728

AC XY:

5396

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.0972

Gnomad4 AMR

AF:

0.0553

Gnomad4 ASJ

AF:

0.0603

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.0474

Gnomad4 FIN

AF:

0.0930

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0710

Bravo

AF:

0.0714

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0677

AC:

261

ESP6500AA

AF:

0.0894

AC:

335

ESP6500EA

AF:

0.0675

AC:

553

ExAC

AF:

0.0614

AC:

7414

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

-0.33

BayesDel_noAF

Benign

-0.17

CADD

Benign

0.61

DEOGEN2

Benign

0.050

T;T;.

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.45

T;.;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Uncertain

0.0092

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.29

MPC

0.15

ClinPred

0.028

GERP RS

-3.0

Varity_R

0.024

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over