dbSNP rs201660431: FIBCD1:p.Arg346Leu (chr9-130905323-C-A) – 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.1037G>T(p.Arg346Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R346H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223

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:

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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=0.19143966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBCD1	NM_032843.5 link	c.1037G>T	p.Arg346Leu	missense_variant	Exon 6 of 7	ENST00000372338.9	NP_116232.3	Q8N539-1
FIBCD1	NM_001145106.2 link	c.1037G>T	p.Arg346Leu	missense_variant	Exon 7 of 8		NP_001138578.1	Q8N539-1
FIBCD1	XM_047423989.1 link	c.1037G>T	p.Arg346Leu	missense_variant	Exon 7 of 8		XP_047279945.1
FIBCD1	XM_047423990.1 link	c.563G>T	p.Arg188Leu	missense_variant	Exon 6 of 7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FIBCD1	ENST00000372338.9 link	c.1037G>T	p.Arg346Leu	missense_variant	Exon 6 of 7	1	NM_032843.5	ENSP00000361413.4	Q8N539-1
FIBCD1	ENST00000448616.5 link	c.1037G>T	p.Arg346Leu	missense_variant	Exon 7 of 8	5		ENSP00000414501.1	Q8N539-1
FIBCD1	ENST00000372337.6 link	c.563G>T	p.Arg188Leu	missense_variant	Exon 6 of 7	5		ENSP00000361412.1	A3KFJ8
FIBCD1	ENST00000444139.5 link	c.806-1251G>T		intron_variant	Intron 4 of 4	2		ENSP00000395319.1	H0Y4Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250078

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.3

DANN

Benign

0.88

DEOGEN2

Benign

0.073

T;T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.76

T;.;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

N;N;.

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.20

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.14

MVP

0.40

MPC

0.15

ClinPred

0.10

GERP RS

-4.9

Varity_R

0.18

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over