9-130905323-C-T

Position:

• chr9-130905323-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_032843.5(FIBCD1):​c.1037G>A​(p.Arg346His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,613,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (1 hom.)
• Consequence: FIBCD1 NM_032843.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.223

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011514574).
• BP6: Variant 9-130905323-C-T is Benign according to our data. Variant chr9-130905323-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2230209.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIBCD1	NM_032843.5	c.1037G>A	p.Arg346His	missense_variant	6/7	ENST00000372338.9	NP_116232.3
FIBCD1	NM_001145106.2	c.1037G>A	p.Arg346His	missense_variant	7/8		NP_001138578.1
FIBCD1	XM_047423989.1	c.1037G>A	p.Arg346His	missense_variant	7/8		XP_047279945.1
FIBCD1	XM_047423990.1	c.563G>A	p.Arg188His	missense_variant	6/7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIBCD1	ENST00000372338.9	c.1037G>A	p.Arg346His	missense_variant	6/7	1	NM_032843.5	ENSP00000361413.4
FIBCD1	ENST00000448616.5	c.1037G>A	p.Arg346His	missense_variant	7/8	5		ENSP00000414501.1
FIBCD1	ENST00000372337.6	c.563G>A	p.Arg188His	missense_variant	6/7	5		ENSP00000361412.1
FIBCD1	ENST00000444139.5	c.806-1251G>A		intron_variant		2		ENSP00000395319.1

Frequencies

GnomAD3 genomes AF: 0.000466 AC: 71 AN: 152214 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00952

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000496 AC: 124 AN: 250078 Hom.: 1 AF XY: 0.000465 AC XY: 63 AN XY: 135450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00558

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000488

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000331 AC: 484 AN: 1461664 Hom.: 1 Cov.: 31 AF XY: 0.000358 AC XY: 260 AN XY: 727126

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00670

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000230

Gnomad4 OTH exome AF: 0.000696

GnomAD4 genome AF: 0.000466 AC: 71 AN: 152214 Hom.: 1 Cov.: 33 AF XY: 0.000403 AC XY: 30 AN XY: 74362

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00952

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000863 Hom.: 0

Bravo AF: 0.000416

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000371 AC: 45

EpiCase AF: 0.000327

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.98
DANN	Benign	0.93
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.74	T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.21	N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.51	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.81	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.079
MVP		0.35
MPC		0.15
ClinPred		0.012	T
GERP RS		-4.9
Varity_R		0.053
gMVP		0.22

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

Other links and lift over

dbSNP: rs201660431; hg19: chr9-133780710;