rs11084377

Variant names:

• chr19-54875434-A-G
• rs11084377
• NM_002000.4:c.70+69A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002000.4. 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
	FCAR	NM_002000.4	MANE Select	c.70+69A>G		intron	N/A	NP_001991.1
	FCAR	NM_133272.4		c.34+1111A>G		intron	N/A	NP_579806.1
	FCAR	NM_133269.4		c.70+69A>G		intron	N/A	NP_579803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.70+69A>G		intron	N/A	ENSP00000347714.3
	FCAR	ENST00000359272.8	TSL:1	c.34+1111A>G		intron	N/A	ENSP00000352218.4
	FCAR	ENST00000391725.7	TSL:1	c.70+69A>G		intron	N/A	ENSP00000375605.3

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

African (AFR) AF: 0.472 AC: 12192 AN: 25836

American (AMR) AF: 0.820 AC: 29851 AN: 36386

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 17373 AN: 22872

East Asian (EAS) AF: 0.912 AC: 34509 AN: 37850

South Asian (SAS) AF: 0.721 AC: 54624 AN: 75794

European-Finnish (FIN) AF: 0.695 AC: 36626 AN: 52688

Middle Eastern (MID) AF: 0.652 AC: 3314 AN: 5080

European-Non Finnish (NFE) AF: 0.678 AC: 571712 AN: 843260

Other (OTH) AF: 0.694 AC: 34446 AN: 49642

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

African (AFR) AF: 0.473 AC: 19605 AN: 41428

American (AMR) AF: 0.726 AC: 11081 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2597 AN: 3468

East Asian (EAS) AF: 0.924 AC: 4764 AN: 5158

South Asian (SAS) AF: 0.706 AC: 3408 AN: 4826

European-Finnish (FIN) AF: 0.693 AC: 7308 AN: 10542

Middle Eastern (MID) AF: 0.645 AC: 187 AN: 290

European-Non Finnish (NFE) AF: 0.669 AC: 45450 AN: 67980

Other (OTH) AF: 0.661 AC: 1393 AN: 2108

Alfa AF: 0.647 Hom.: 11531

Bravo AF: 0.634

Asia WGS AF: 0.808 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.51
PhyloP100		0.10
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: rs11084377; hg19: chr19-55386890;