chr1-159307919-C-T

Position:

• chr1-159307919-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001387280.1(FCER1A):​c.761C>T​(p.Pro254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,589,846 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (12 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.368

Genes affected

FCER1A (HGNC:3609): (Fc epsilon receptor Ia) The immunoglobulin epsilon receptor (IgE receptor) is the initiator of the allergic response. When two or more high-affinity IgE receptors are brought together by allergen-bound IgE molecules, mediators such as histamine that are responsible for allergy symptoms are released. This receptor is comprised of an alpha subunit, a beta subunit, and two gamma subunits. The protein encoded by this gene represents the alpha subunit. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005096704).
• BP6: Variant 1-159307919-C-T is Benign according to our data. Variant chr1-159307919-C-T is described in ClinVar as [Benign]. Clinvar id is 785791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER1A	NM_001387280.1	c.761C>T	p.Pro254Leu	missense_variant	5/5	ENST00000693622.1
FCER1A	NM_002001.4	c.761C>T	p.Pro254Leu	missense_variant	7/7
FCER1A	NM_001387282.1	c.662C>T	p.Pro221Leu	missense_variant	5/5
FCER1A	NM_001387281.1	c.506C>T	p.Pro169Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER1A	ENST00000693622.1	c.761C>T	p.Pro254Leu	missense_variant	5/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5	c.761C>T	p.Pro254Leu	missense_variant	6/6	1		P1
FCER1A	ENST00000368114.1	c.662C>T	p.Pro221Leu	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00168 AC: 410 AN: 243372 Hom.: 7 AF XY: 0.00177 AC XY: 232 AN XY: 131416

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.000859

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000350

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000810

Gnomad OTH exome AF: 0.00339

GnomAD4 exome AF: 0.00101 AC: 1457 AN: 1437568 Hom.: 12 Cov.: 30 AF XY: 0.00103 AC XY: 732 AN XY: 711864

Gnomad4 AFR exome AF: 0.000335

Gnomad4 AMR exome AF: 0.000860

Gnomad4 ASJ exome AF: 0.0264

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000959

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000489

Gnomad4 OTH exome AF: 0.00294

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74458

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00192 Hom.: 6

Bravo AF: 0.00145

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00126 AC: 153

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.0051	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.023
Sift	Benign	0.21	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0050	B;.
Vest4		0.15
MVP		0.19
MPC		0.024
ClinPred		0.015	T
GERP RS		-0.15
Varity_R		0.035
gMVP		0.34

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: rs143419433; hg19: chr1-159277709; COSMIC: COSV104426585;