rs766248349

Variant names:

• chr9-130904147-C-G
• rs766248349
• NM_032843.5:c.1303G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-130904147-C-G
• chr9-130904147-C-T

Variant summary

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

The NM_032843.5(FIBCD1):​c.1303G>C​(p.Val435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. V435M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FIBCD1 NM_032843.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 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 rank	MANE	Protein	UniProt
FIBCD1	NM_032843.5	c.1303G>C	p.Val435Leu	missense_variant	Exon 7 of 7	ENST00000372338.9	NP_116232.3
FIBCD1	NM_001145106.2	c.1303G>C	p.Val435Leu	missense_variant	Exon 8 of 8		NP_001138578.1
FIBCD1	XM_047423989.1	c.1303G>C	p.Val435Leu	missense_variant	Exon 8 of 8		XP_047279945.1
FIBCD1	XM_047423990.1	c.829G>C	p.Val277Leu	missense_variant	Exon 7 of 7		XP_047279946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBCD1	ENST00000372338.9	c.1303G>C	p.Val435Leu	missense_variant	Exon 7 of 7	1	NM_032843.5	ENSP00000361413.4
FIBCD1	ENST00000448616.5	c.1303G>C	p.Val435Leu	missense_variant	Exon 8 of 8	5		ENSP00000414501.1
FIBCD1	ENST00000372337.6	c.829G>C	p.Val277Leu	missense_variant	Exon 7 of 7	5		ENSP00000361412.1
FIBCD1	ENST00000444139.5	c.806-75G>C		intron_variant	Intron 4 of 4	2		ENSP00000395319.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250750 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135724

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D;.;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.12	B;B;.
Vest4		0.22
MutPred		0.78		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.72
MPC		0.25
ClinPred		0.78	D
GERP RS		1.3
Varity_R		0.50
gMVP		0.34

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: rs766248349; hg19: chr9-133779534;