19-18588898-T-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100418.2(REX1BD):c.97T>C(p.Trp33Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,379,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W33G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

REX1BD
NM_001100418.2 missense, splice_region

Scores

Splicing: ADA: 0.0006208

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.634

Publications

0 publications found

Variant links:

Genes affected

REX1BD (HGNC:26098): (required for excision 1-B domain containing)

REX1BD links:

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

CRLF1 Gene-Disease associations (from GenCC):

Cold-induced sweating syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
cold-induced sweating syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
idiopathic achalasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CRLF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20102486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REX1BD	NM_001100418.2 link	c.97T>C	p.Trp33Arg	missense_variant, splice_region_variant	Exon 1 of 5	ENST00000358607.11	NP_001093888.1	Q96EN9-1
REX1BD	NM_001100419.2 link	c.97T>C	p.Trp33Arg	missense_variant, splice_region_variant	Exon 1 of 5		NP_001093889.1	Q96EN9-3
REX1BD	XM_047439026.1 link	c.-297T>C		upstream_gene_variant			XP_047294982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REX1BD	ENST00000358607.11 link	c.97T>C	p.Trp33Arg	missense_variant, splice_region_variant	Exon 1 of 5	1	NM_001100418.2	ENSP00000351422.5		Q96EN9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000789

AC:

AN:

126808

AF XY:

0.0000144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000988

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1379140

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

680706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31054

American (AMR)

AF:

0.00

AC:

AN:

35516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25016

East Asian (EAS)

AF:

0.0000282

AC:

AN:

35436

South Asian (SAS)

AF:

0.00

AC:

AN:

78938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077206

Other (OTH)

AF:

0.00

AC:

AN:

57526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

0.092

Eigen_PC

Benign

-0.030

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.67

PhyloP100

0.63

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.22

MutPred

0.42

Gain of disorder (P = 0.0093);Gain of disorder (P = 0.0093);

MVP

0.57

MPC

1.7

ClinPred

0.96

GERP RS

2.5

PromoterAI

-0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00062

dbscSNV1_RF

Benign

0.010

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

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19-18588898-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over