19-7690583-T-C

Variant names:

• chr19-7690583-T-C
• rs2277995
• NM_001220500.2:c.470-26A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001220500.2(FCER2):​c.470-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,603,798 control chromosomes in the GnomAD database, including 72,819 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.35 (10335 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62484 hom.)
• Consequence: FCER2 NM_001220500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 4 publications found

Genes affected

FCER2 (HGNC:3612): (Fc epsilon receptor II) The protein encoded by this gene is a B-cell specific antigen, and a low-affinity receptor for IgE. It has essential roles in B cell growth and differentiation, and the regulation of IgE production. This protein also exists as a soluble secreted form, then functioning as a potent mitogenic growth factor. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.470-26A>G		intron_variant	Intron 8 of 10	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.470-26A>G		intron_variant	Intron 8 of 10		NP_001993.2
FCER2	NM_001207019.3	c.467-26A>G		intron_variant	Intron 7 of 9		NP_001193948.2
FCER2	XM_005272462.5	c.470-26A>G		intron_variant	Intron 8 of 10		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.470-26A>G		intron_variant	Intron 8 of 10	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52891 AN: 151530 Hom.: 10314 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.349

GnomAD2 exomes AF: 0.294 AC: 70971 AN: 241500 AF XY: 0.298

Gnomad AFR exome AF: 0.532

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.365

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.288 AC: 417523 AN: 1452150 Hom.: 62484 Cov.: 34 AF XY: 0.290 AC XY: 209514 AN XY: 722120

African (AFR) AF: 0.546 AC: 18196 AN: 33340

American (AMR) AF: 0.170 AC: 7516 AN: 44180

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 8307 AN: 25856

East Asian (EAS) AF: 0.294 AC: 11633 AN: 39542

South Asian (SAS) AF: 0.363 AC: 31106 AN: 85578

European-Finnish (FIN) AF: 0.227 AC: 11630 AN: 51180

Middle Eastern (MID) AF: 0.385 AC: 2191 AN: 5688

European-Non Finnish (NFE) AF: 0.279 AC: 308358 AN: 1106776

Other (OTH) AF: 0.310 AC: 18586 AN: 60010

GnomAD4 genome AF: 0.349 AC: 52942 AN: 151648 Hom.: 10335 Cov.: 32 AF XY: 0.346 AC XY: 25625 AN XY: 74110

African (AFR) AF: 0.528 AC: 21797 AN: 41310

American (AMR) AF: 0.254 AC: 3882 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1101 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1762 AN: 5126

South Asian (SAS) AF: 0.378 AC: 1816 AN: 4810

European-Finnish (FIN) AF: 0.228 AC: 2400 AN: 10536

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19035 AN: 67828

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.325 Hom.: 1503

Bravo AF: 0.356

Asia WGS AF: 0.346 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.44
PhyloP100		-3.0
BranchPoint Hunter		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2277995; hg19: chr19-7755469;