14-105769274-A-T

Variant summary

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

The ENST00000641136.1(IGHG3):c.1097T>A(p.Phe366Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 757,316 control chromosomes in the GnomAD database, including 57,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (7624 hom., cov: 30)
  • Exomes 𝑓: 0.36 (49574 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

Genes affected

IGHG3 (HGNC:5527): (immunoglobulin heavy constant gamma 3 (G3m marker)) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Involved in retina homeostasis. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHG3	ENST00000641136.1	c.1097T>A	p.Phe366Tyr	missense_variant	7/9			P5
IGHG3	ENST00000390551.6	c.1097T>A	p.Phe366Tyr	missense_variant	7/7			A2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 44782 AN: 132500 Hom.: 7602 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.330

GnomAD3 exomes AF: 0.416 AC: 92368 AN: 221858 Hom.: 21121 AF XY: 0.409 AC XY: 49144 AN XY: 120096

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.444

Gnomad SAS exome AF: 0.474

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.363 AC: 226477 AN: 624748 Hom.: 49574 Cov.: 0 AF XY: 0.358 AC XY: 121963 AN XY: 340462

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.628

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.722

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.338 AC: 44831 AN: 132568 Hom.: 7624 Cov.: 30 AF XY: 0.355 AC XY: 22987 AN XY: 64804

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.330

Alfa AF: 0.202 Hom.: 569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	5.9
Dann	Benign	0.45

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: rs1051112; hg19: chr14-106235611;