Variant 9-130904275-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032843.5(FIBCD1):c.1175G>A(p.Arg392His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,322 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FIBCD1
NM_032843.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIBCD1	NM_032843.5 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	7/7	ENST00000372338.9	NP_116232.3	Q8N539-1
FIBCD1	NM_001145106.2 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	8/8		NP_001138578.1	Q8N539-1
FIBCD1	XM_047423989.1 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	8/8		XP_047279945.1
FIBCD1	XM_047423990.1 linkuse as main transcript	c.701G>A	p.Arg234His	missense_variant	7/7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FIBCD1	ENST00000372338.9 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	7/7	1	NM_032843.5	ENSP00000361413.4	Q8N539-1
FIBCD1	ENST00000448616.5 linkuse as main transcript	c.1175G>A	p.Arg392His	missense_variant	8/8	5		ENSP00000414501.1	Q8N539-1
FIBCD1	ENST00000372337.6 linkuse as main transcript	c.701G>A	p.Arg234His	missense_variant	7/7	5		ENSP00000361412.1	A3KFJ8
FIBCD1	ENST00000444139.5 linkuse as main transcript	c.806-203G>A		intron_variant		2		ENSP00000395319.1	H0Y4Y8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249096

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1461150

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

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

Sep 20, 2024

The c.1175G>A (p.R392H) 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 1175, causing the arginine (R) at amino acid position 392 to be replaced by a histidine (H). 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

0.091

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.078

T;T;.

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.099

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.59

P;P;.

Vest4

0.24

MutPred

0.71

Loss of phosphorylation at S394 (P = 0.0662);Loss of phosphorylation at S394 (P = 0.0662);.;

MVP

0.76

MPC

0.59

ClinPred

0.90

GERP RS

2.5

Varity_R

0.18

gMVP

0.37

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