rs741143

Positions:

• chr19-39872380-G-A
• chr19-39872380-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003890.3(FCGBP):​c.11486C>T​(p.Ala3829Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,365,360 control chromosomes in the GnomAD database, including 31,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3758 hom., cov: 33)
  • Exomes 𝑓: 0.21 (28226 hom.)
• Consequence: FCGBP NM_003890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

Genes affected

FCGBP (HGNC:13572): (Fc gamma binding protein) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGBP	NM_003890.3	c.11486C>T	p.Ala3829Val	missense_variant	32/36		NP_003881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGBP	ENST00000616721.6	c.11447C>T	p.Ala3816Val	missense_variant	24/28	1		ENSP00000481056.3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32016 AN: 152010 Hom.: 3758 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.235 AC: 56626 AN: 241416 Hom.: 7657 AF XY: 0.238 AC XY: 31313 AN XY: 131680

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.274

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.209 AC: 253925 AN: 1213232 Hom.: 28226 Cov.: 33 AF XY: 0.213 AC XY: 128085 AN XY: 601236

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.211 AC: 32030 AN: 152128 Hom.: 3758 Cov.: 33 AF XY: 0.212 AC XY: 15735 AN XY: 74372

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.224

Alfa AF: 0.212 Hom.: 6334

Bravo AF: 0.212

Asia WGS AF: 0.390 AC: 1351 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.23
DANN	Benign	0.45

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: rs741143; hg19: chr19-40363020;