Genetic Variant CRLF3:p.Glu8Asp (chr17-30824628-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_015986.4(CRLF3):c.24G>C(p.Glu8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CRLF3
NM_015986.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.435

Publications

0 publications found

Variant links:

Genes affected

CRLF3 (HGNC:17177): (cytokine receptor like factor 3) This gene encodes a cytokine receptor-like factor that may negatively regulate cell cycle progression at the G0/G1 phase. Studies of the related rat protein suggest that it may regulate neuronal morphology and synaptic vesicle biogenesis. This gene is one of several genes located in the neurofibromatosis type I tumor suppressor region on the q arm of chromosome 17, a region that is subject to microdeletions, duplications, chromosomal breaks and rearrangements. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2 and 5. [provided by RefSeq, Aug 2012]

CRLF3 links:

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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=0.15599263).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015986.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF3	NM_015986.4	MANE Select	c.24G>C	p.Glu8Asp	missense	Exon 1 of 8	NP_057070.3
	CRLF3	NR_073118.2		n.65G>C		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRLF3	ENST00000324238.7	TSL:1 MANE Select	c.24G>C	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000318804.6	Q8IUI8-1
CRLF3	ENST00000921129.1		c.24G>C	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000591188.1
CRLF3	ENST00000885412.1		c.24G>C	p.Glu8Asp	missense	Exon 1 of 8	ENSP00000555471.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000881

AC:

AN:

227042

AF XY:

0.00000796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1449786

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32894

American (AMR)

AF:

0.0000450

AC:

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

39258

South Asian (SAS)

AF:

0.00

AC:

AN:

85684

European-Finnish (FIN)

AF:

0.0000218

AC:

AN:

45822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1110054

Other (OTH)

AF:

0.00

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.55

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.43

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Benign

0.037

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.036

Polyphen

0.60

Vest4

0.22

MutPred

0.18

Loss of helix (P = 0.0196)

MVP

0.17

MPC

0.28

ClinPred

0.55

GERP RS

2.0

PromoterAI

0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.36

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over