rs7258589

Variant names:

• chr19-18590689-C-T
• rs7258589
• NM_001100418.2:c.454-165C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100418.2(REX1BD):​c.454-165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 614,636 control chromosomes in the GnomAD database, including 16,220 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3447 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12773 hom.)
• Consequence: REX1BD NM_001100418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 15 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REX1BD	NM_001100418.2	c.454-165C>T		intron_variant	Intron 3 of 4	ENST00000358607.11	NP_001093888.1
REX1BD	NM_001100419.2	c.388-165C>T		intron_variant	Intron 3 of 4		NP_001093889.1
REX1BD	XM_047439026.1	c.490-165C>T		intron_variant	Intron 1 of 2		XP_047294982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REX1BD	ENST00000358607.11	c.454-165C>T		intron_variant	Intron 3 of 4	1	NM_001100418.2	ENSP00000351422.5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29364 AN: 152092 Hom.: 3445 Cov.: 33

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.226 AC: 104368 AN: 462426 Hom.: 12773 Cov.: 6 AF XY: 0.223 AC XY: 54031 AN XY: 242576

African (AFR) AF: 0.0844 AC: 970 AN: 11488

American (AMR) AF: 0.112 AC: 1987 AN: 17786

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 2941 AN: 13452

East Asian (EAS) AF: 0.106 AC: 2927 AN: 27518

South Asian (SAS) AF: 0.163 AC: 7378 AN: 45364

European-Finnish (FIN) AF: 0.328 AC: 9512 AN: 29030

Middle Eastern (MID) AF: 0.162 AC: 519 AN: 3204

European-Non Finnish (NFE) AF: 0.252 AC: 72631 AN: 288554

Other (OTH) AF: 0.211 AC: 5503 AN: 26030

GnomAD4 genome AF: 0.193 AC: 29355 AN: 152210 Hom.: 3447 Cov.: 33 AF XY: 0.195 AC XY: 14491 AN XY: 74418

African (AFR) AF: 0.0839 AC: 3486 AN: 41548

American (AMR) AF: 0.144 AC: 2207 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 688 AN: 3466

East Asian (EAS) AF: 0.121 AC: 627 AN: 5174

South Asian (SAS) AF: 0.156 AC: 755 AN: 4832

European-Finnish (FIN) AF: 0.332 AC: 3509 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17415 AN: 68000

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.222 Hom.: 11766

Bravo AF: 0.174

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		0.011
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7258589; hg19: chr19-18701499;