9-130924234-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_032843.5(FIBCD1):c.712+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,586,494 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (15 hom.)
• Consequence: FIBCD1 NM_032843.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0007164
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.540

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 9-130924234-C-T is Benign according to our data. Variant chr9-130924234-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIBCD1	NM_032843.5	c.712+3G>A		splice_donor_region_variant, intron_variant		ENST00000372338.9
FIBCD1	NM_001145106.2	c.712+3G>A		splice_donor_region_variant, intron_variant
FIBCD1	XM_047423989.1	c.712+3G>A		splice_donor_region_variant, intron_variant
FIBCD1	XM_047423990.1	c.238+3G>A		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBCD1	ENST00000372338.9	c.712+3G>A		splice_donor_region_variant, intron_variant		1	NM_032843.5	P1

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152108 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00512

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00273 AC: 566 AN: 207236 Hom.: 1 AF XY: 0.00271 AC XY: 309 AN XY: 113828

Gnomad AFR exome AF: 0.000663

Gnomad AMR exome AF: 0.00395

Gnomad ASJ exome AF: 0.00287

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000380

Gnomad FIN exome AF: 0.00185

Gnomad NFE exome AF: 0.00401

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00433 AC: 6213 AN: 1434268 Hom.: 15 Cov.: 32 AF XY: 0.00410 AC XY: 2912 AN XY: 710678

Gnomad4 AFR exome AF: 0.000575

Gnomad4 AMR exome AF: 0.00478

Gnomad4 ASJ exome AF: 0.00268

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.0000608

Gnomad4 FIN exome AF: 0.00216

Gnomad4 NFE exome AF: 0.00502

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.00365 AC: 555 AN: 152226 Hom.: 3 Cov.: 33 AF XY: 0.00333 AC XY: 248 AN XY: 74434

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00398 Hom.: 0

Bravo AF: 0.00425

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

FIBCD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	18
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00072
dbscSNV1_RF	Benign	0.048
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: rs184563385; hg19: chr9-133799621; COSMIC: COSV99447449;