19-39872380-G-C

Variant names:

• chr19-39872380-G-C
• rs741143
• NM_003890.3:c.11486C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003890.3(FCGBP):​c.11486C>G​(p.Ala3829Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,213,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A3829T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: FCGBP NM_003890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 27 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGBP	NM_003890.3	MANE Select	c.11486C>G	p.Ala3829Gly	missense	Exon 32 of 36	NP_003881.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGBP	ENST00000616721.6	TSL:1	c.11447C>G	p.Ala3816Gly	missense	Exon 24 of 28	ENSP00000481056.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.000128 AC: 31 AN: 241416 AF XY: 0.000122

Gnomad AFR exome AF: 0.000199

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.000623

Gnomad FIN exome AF: 0.0000959

Gnomad NFE exome AF: 0.0000836

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.0000338 AC: 41 AN: 1213346 Hom.: 0 Cov.: 33 AF XY: 0.0000482 AC XY: 29 AN XY: 601292

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000761 AC: 2 AN: 26270

American (AMR) AF: 0.00 AC: 0 AN: 36948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16864

East Asian (EAS) AF: 0.00144 AC: 24 AN: 16650

South Asian (SAS) AF: 0.00 AC: 0 AN: 83150

European-Finnish (FIN) AF: 0.0000312 AC: 1 AN: 32022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4464

European-Non Finnish (NFE) AF: 0.0000147 AC: 14 AN: 953114

Other (OTH) AF: 0.00 AC: 0 AN: 43864

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	0.98
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs741143; hg19: chr19-40363020;