rs741143

Variant names:

• chr19-39872380-G-A
• rs741143
• ENST00000616721.6:c.11447C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000616721.6(FCGBP):​c.11447C>T​(p.Ala3816Val) 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. 6/8 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. A3816T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.21 (3758 hom., cov: 33)
  • Exomes 𝑓: 0.21 (28226 hom.)
• Consequence: FCGBP ENST00000616721.6 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.095).
• 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 rank	MANE	Protein	UniProt
FCGBP	NM_003890.3	c.11486C>T	p.Ala3829Val	missense_variant	Exon 32 of 36		NP_003881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGBP	ENST00000616721.6	c.11447C>T	p.Ala3816Val	missense_variant	Exon 24 of 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

GnomAD2 exomes AF: 0.235 AC: 56626 AN: 241416 AF XY: 0.238

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 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

African (AFR) AF: 0.178 AC: 4676 AN: 26270

American (AMR) AF: 0.160 AC: 5907 AN: 36920

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 4433 AN: 16862

East Asian (EAS) AF: 0.552 AC: 9182 AN: 16638

South Asian (SAS) AF: 0.274 AC: 22803 AN: 83140

European-Finnish (FIN) AF: 0.179 AC: 5740 AN: 32016

Middle Eastern (MID) AF: 0.243 AC: 1085 AN: 4464

European-Non Finnish (NFE) AF: 0.199 AC: 190065 AN: 953058

Other (OTH) AF: 0.229 AC: 10034 AN: 43864

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

African (AFR) AF: 0.187 AC: 7781 AN: 41510

American (AMR) AF: 0.189 AC: 2886 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2858 AN: 5148

South Asian (SAS) AF: 0.292 AC: 1411 AN: 4828

European-Finnish (FIN) AF: 0.164 AC: 1738 AN: 10604

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13704 AN: 67958

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.213 Hom.: 9010

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
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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;