chr19-18590689-C-T

Position:

• chr19-18590689-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
REX1BD	NM_001100418.2	c.454-165C>T		intron_variant		ENST00000358607.11	NP_001093888.1
REX1BD	NM_001100419.2	c.388-165C>T		intron_variant			NP_001093889.1
REX1BD	XM_047439026.1	c.490-165C>T		intron_variant			XP_047294982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REX1BD	ENST00000358607.11	c.454-165C>T		intron_variant		1	NM_001100418.2	ENSP00000351422

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

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.211

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

Gnomad4 AFR AF: 0.0839

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.181

Alfa AF: 0.233 Hom.: 7591

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

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

Other links and lift over

dbSNP: rs7258589; hg19: chr19-18701499;