Genetic Variant FIBCD1:p.Glu459Lys (chr9-130904075-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032843.5(FIBCD1):c.1375G>A(p.Glu459Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

Variant links:

Genes affected

FIBCD1 (HGNC:25922): (fibrinogen C domain containing 1) FIBCD1 is a conserved type II transmembrane endocytic receptor that binds chitin and is located primarily in the intestinal brush border (Schlosser et al., 2009 [PubMed 19710473]).[supplied by OMIM, Apr 2010]

FIBCD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26023597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBCD1	NM_032843.5 link	c.1375G>A	p.Glu459Lys	missense_variant	Exon 7 of 7	ENST00000372338.9	NP_116232.3	Q8N539-1
FIBCD1	NM_001145106.2 link	c.1375G>A	p.Glu459Lys	missense_variant	Exon 8 of 8		NP_001138578.1	Q8N539-1
FIBCD1	XM_047423989.1 link	c.1375G>A	p.Glu459Lys	missense_variant	Exon 8 of 8		XP_047279945.1
FIBCD1	XM_047423990.1 link	c.901G>A	p.Glu301Lys	missense_variant	Exon 7 of 7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FIBCD1	ENST00000372338.9 link	c.1375G>A	p.Glu459Lys	missense_variant	Exon 7 of 7	1	NM_032843.5	ENSP00000361413.4	Q8N539-1
FIBCD1	ENST00000448616.5 link	c.1375G>A	p.Glu459Lys	missense_variant	Exon 8 of 8	5		ENSP00000414501.1	Q8N539-1
FIBCD1	ENST00000372337.6 link	c.901G>A	p.Glu301Lys	missense_variant	Exon 7 of 7	5		ENSP00000361412.1	A3KFJ8
FIBCD1	ENST00000444139.5 link	c.806-3G>A		splice_region_variant, intron_variant	Intron 4 of 4	2		ENSP00000395319.1	H0Y4Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246830

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS 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:

6.85e-7

AC:

AN:

1460368

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1375G>A (p.E459K) alteration is located in exon 7 (coding exon 7) of the FIBCD1 gene. This alteration results from a G to A substitution at nucleotide position 1375, causing the glutamic acid (E) at amino acid position 459 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.93

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.025

D;D;T

Polyphen

0.32

B;B;.

Vest4

0.46

MutPred

0.36

Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);.;

MVP

0.58

MPC

0.26

ClinPred

0.44

GERP RS

3.7

Varity_R

0.30

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over