rs11084377

Positions:

• chr19-54875434-A-G
• chr19-54875434-A-T

Variant summary

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

The NM_002000.4(FCAR):​c.70+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,301,382 control chromosomes in the GnomAD database, including 308,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (31488 hom., cov: 31)
  • Exomes 𝑓: 0.69 (276837 hom.)
• Consequence: FCAR NM_002000.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

FCAR (HGNC:3608): (Fc alpha receptor) This gene is a member of the immunoglobulin gene superfamily and encodes a receptor for the Fc region of IgA. The receptor is a transmembrane glycoprotein present on the surface of myeloid lineage cells such as neutrophils, monocytes, macrophages, and eosinophils, where it mediates immunologic responses to pathogens. It interacts with IgA-opsonized targets and triggers several immunologic defense processes, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and stimulation of the release of inflammatory mediators. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.70+69A>G		intron_variant		ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.70+69A>G		intron_variant		1	NM_002000.4	ENSP00000347714	P2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96280 AN: 151856 Hom.: 31457 Cov.: 31

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.691 AC: 794647 AN: 1149408 Hom.: 276837 AF XY: 0.691 AC XY: 404661 AN XY: 585624

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.760

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.678

Gnomad4 OTH exome AF: 0.694

GnomAD4 genome AF: 0.634 AC: 96357 AN: 151974 Hom.: 31488 Cov.: 31 AF XY: 0.641 AC XY: 47603 AN XY: 74288

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.661

Alfa AF: 0.646 Hom.: 7016

Bravo AF: 0.634

Asia WGS AF: 0.808 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.51

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: rs11084377; hg19: chr19-55386890;