chr19-18589641-C-A

Variant names:

• chr19-18589641-C-A
• rs879685326
• NM_001100418.2:c.411C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001100418.2(REX1BD):​c.411C>A​(p.His137Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,359,940 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: REX1BD NM_001100418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REX1BD	NM_001100418.2	c.411C>A	p.His137Gln	missense_variant	Exon 3 of 5	ENST00000358607.11	NP_001093888.1
REX1BD	NM_001100419.2	c.345C>A	p.His115Gln	missense_variant	Exon 3 of 5		NP_001093889.1
REX1BD	XM_047439026.1	c.447C>A	p.His149Gln	missense_variant	Exon 1 of 3		XP_047294982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REX1BD	ENST00000358607.11	c.411C>A	p.His137Gln	missense_variant	Exon 3 of 5	1	NM_001100418.2	ENSP00000351422.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000944 AC: 1 AN: 105970 Hom.: 0 AF XY: 0.0000173 AC XY: 1 AN XY: 57766

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000368 AC: 5 AN: 1359940 Hom.: 0 Cov.: 34 AF XY: 0.00000448 AC XY: 3 AN XY: 669614

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000467

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	0.0051	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.81	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.19
Sift	Benign	0.070	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.26		Loss of helix (P = 0.0167);.;
MVP		0.43
MPC		1.3
ClinPred		0.96	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.42
gMVP		0.23

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: rs879685326; hg19: chr19-18700451;