rs28364072

Variant names:

• chr19-7690399-A-G
• rs28364072
• NM_001220500.2:c.621+7T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7690399-A-G
• chr19-7690399-A-T

Variant summary

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

The NM_001220500.2(FCER2):​c.621+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,612,512 control chromosomes in the GnomAD database, including 72,921 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10842 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62079 hom.)
• Consequence: FCER2 NM_001220500.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001808
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 44 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: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.621+7T>C		splice_region_variant, intron_variant	Intron 9 of 10	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.621+7T>C		splice_region_variant, intron_variant	Intron 9 of 10		NP_001993.2
FCER2	NM_001207019.3	c.618+7T>C		splice_region_variant, intron_variant	Intron 8 of 9		NP_001193948.2
FCER2	XM_005272462.5	c.621+7T>C		splice_region_variant, intron_variant	Intron 9 of 10		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.621+7T>C		splice_region_variant, intron_variant	Intron 9 of 10	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53755 AN: 151856 Hom.: 10814 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.293 AC: 73199 AN: 250108 AF XY: 0.296

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.296

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.286 AC: 417076 AN: 1460538 Hom.: 62079 Cov.: 37 AF XY: 0.288 AC XY: 209081 AN XY: 726458

African (AFR) AF: 0.569 AC: 19029 AN: 33460

American (AMR) AF: 0.169 AC: 7545 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7855 AN: 26078

East Asian (EAS) AF: 0.295 AC: 11695 AN: 39668

South Asian (SAS) AF: 0.355 AC: 30568 AN: 86192

European-Finnish (FIN) AF: 0.231 AC: 12277 AN: 53194

Middle Eastern (MID) AF: 0.369 AC: 2125 AN: 5754

European-Non Finnish (NFE) AF: 0.277 AC: 307429 AN: 1111208

Other (OTH) AF: 0.308 AC: 18553 AN: 60310

GnomAD4 genome AF: 0.354 AC: 53815 AN: 151974 Hom.: 10842 Cov.: 32 AF XY: 0.351 AC XY: 26061 AN XY: 74320

African (AFR) AF: 0.552 AC: 22860 AN: 41438

American (AMR) AF: 0.253 AC: 3870 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1768 AN: 5156

South Asian (SAS) AF: 0.369 AC: 1778 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2468 AN: 10580

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18880 AN: 67916

Other (OTH) AF: 0.346 AC: 731 AN: 2110

Alfa AF: 0.295 Hom.: 13373

Bravo AF: 0.361

Asia WGS AF: 0.343 AC: 1191 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs28364072; hg19: chr19-7755285; COSMIC: COSV60916301; COSMIC: COSV60916301;