Variant 9-130905309-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032843.5(FIBCD1):c.1051G>A(p.Gly351Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,856 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048562765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FIBCD1	NM_032843.5 linkuse as main transcript	c.1051G>A	p.Gly351Ser	missense_variant	6/7	ENST00000372338.9
FIBCD1	NM_001145106.2 linkuse as main transcript	c.1051G>A	p.Gly351Ser	missense_variant	7/8
FIBCD1	XM_047423989.1 linkuse as main transcript	c.1051G>A	p.Gly351Ser	missense_variant	7/8
FIBCD1	XM_047423990.1 linkuse as main transcript	c.577G>A	p.Gly193Ser	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBCD1	ENST00000372338.9 linkuse as main transcript	c.1051G>A	p.Gly351Ser	missense_variant	6/7	1	NM_032843.5	P1	Q8N539-1
FIBCD1	ENST00000448616.5 linkuse as main transcript	c.1051G>A	p.Gly351Ser	missense_variant	7/8	5		P1	Q8N539-1
FIBCD1	ENST00000372337.6 linkuse as main transcript	c.577G>A	p.Gly193Ser	missense_variant	6/7	5
FIBCD1	ENST00000444139.5 linkuse as main transcript	c.808-1237G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000440

AC:

AN:

250064

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1051G>A (p.G351S) alteration is located in exon 6 (coding exon 6) of the FIBCD1 gene. This alteration results from a G to A substitution at nucleotide position 1051, causing the glycine (G) at amino acid position 351 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

Cadd

Benign

7.6

Dann

Benign

0.93

DEOGEN2

Benign

0.013

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.9

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.050

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.56

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.042

B;B;.

Vest4

0.22

MVP

0.13

MPC

0.12

ClinPred

0.012

GERP RS

3.2

Varity_R

0.15

gMVP

0.57

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