X-1202479-C-T

Position:

chrX-1202479-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_022148.4(CRLF2):c.406G>A(p.Val136Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,613,560 control chromosomes in the GnomAD database, including 467 homozygotes. There are 17,220 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.019 ( 38 hom., 1356 hem., cov: 31)

Exomes 𝑓: 0.022 ( 429 hom. 15864 hem. )

Consequence

CRLF2
NM_022148.4 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.0690

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035479069).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0194 (2957/152250) while in subpopulation NFE AF= 0.0231 (1568/68008). AF 95% confidence interval is 0.0221. There are 38 homozygotes in gnomad4. There are 1356 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRLF2	NM_022148.4 linkuse as main transcript	c.406G>A	p.Val136Met	missense_variant	4/8	ENST00000400841.8	NP_071431.2	Q9HC73-1D0E2W4
CRLF2	NM_001012288.3 linkuse as main transcript	c.70G>A	p.Val24Met	missense_variant	3/7		NP_001012288.2	Q9HC73-3
CRLF2	XM_011546181.3 linkuse as main transcript	c.403G>A	p.Val135Met	missense_variant	4/8		XP_011544483.1
CRLF2	NR_110830.2 linkuse as main transcript	n.418G>A		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CRLF2	ENST00000400841.8 linkuse as main transcript	c.406G>A	p.Val136Met	missense_variant	4/8	1	NM_022148.4	ENSP00000383641.3	Q9HC73-1
CRLF2	ENST00000381567.8 linkuse as main transcript	c.70G>A	p.Val24Met	missense_variant	3/7	1		ENSP00000370979.4	Q9HC73-3
CRLF2	ENST00000467626.6 linkuse as main transcript	n.403G>A		non_coding_transcript_exon_variant	4/8	5		ENSP00000485269.1	A0A0C4DH06

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2955

AN:

152132

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1355

AN XY:

74308

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0686

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0254

GnomAD3 exomes

AF:

0.0176

AC:

4374

AN:

248930

Hom.:

AF XY:

0.0175

AC XY:

2369

AN XY:

135034

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.00968

Gnomad ASJ exome

AF:

0.0642

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0222

AC:

32421

AN:

1461310

Hom.:

429

Cov.:

AF XY:

0.0218

AC XY:

15864

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00275

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0228

GnomAD4 genome

AF:

0.0194

AC:

2957

AN:

152250

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1356

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.0686

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0114

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0251

Bravo

AF:

0.0209

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0252

AC:

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0256

AC:

215

ExAC

AF:

0.0176

AC:

2131

EpiCase

AF:

0.0241

EpiControl

AF:

0.0261

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

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;T;.

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.64

T;.;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

2.0

M;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.54

N;N;.

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.13

MPC

0.38

ClinPred

0.034

GERP RS

0.32

Varity_R

0.10

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