Variant 9-130904153-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032843.5(FIBCD1):c.1297G>A(p.Asp433Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,613,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 1 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39632288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FIBCD1	NM_032843.5 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	7/7	ENST00000372338.9
FIBCD1	NM_001145106.2 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	8/8
FIBCD1	XM_047423989.1 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	8/8
FIBCD1	XM_047423990.1 linkuse as main transcript	c.823G>A	p.Asp275Asn	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBCD1	ENST00000372338.9 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	7/7	1	NM_032843.5	P1	Q8N539-1
FIBCD1	ENST00000448616.5 linkuse as main transcript	c.1297G>A	p.Asp433Asn	missense_variant	8/8	5		P1	Q8N539-1
FIBCD1	ENST00000372337.6 linkuse as main transcript	c.823G>A	p.Asp275Asn	missense_variant	7/7	5
FIBCD1	ENST00000444139.5 linkuse as main transcript	c.808-81G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000957

AC:

AN:

250814

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.000116

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1461276

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.000112

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:

0.0000207

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000263

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000727

Hom.:

Bravo

AF:

0.000283

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 06, 2021

The c.1297G>A (p.D433N) 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 1297, causing the aspartic acid (D) at amino acid position 433 to be replaced by an asparagine (N). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.026

T;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;.;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.47

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.40

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.95

P;P;.

Vest4

0.76

MVP

0.80

MPC

0.54

ClinPred

0.17

GERP RS

3.8

Varity_R

0.50

gMVP

0.62

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