rs4042056

Positions:

• chr14-105769277-C-T

Variant summary

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

The ENST00000641136.1(IGHG3):​c.1094G>A​(p.Arg365His) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.097 (165 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1362 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662

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=-0.95).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.1094G>A	p.Arg365His	missense_variant	7/9			P5
IGHG3	ENST00000390551.6	c.1094G>A	p.Arg365His	missense_variant	7/7			A2

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 10827 AN: 111498 Hom.: 162 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0218

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0394

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0870

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0914

GnomAD4 exome AF: 0.0306 AC: 18364 AN: 600176 Hom.: 1362 Cov.: 0 AF XY: 0.0334 AC XY: 10946 AN XY: 327884

Gnomad4 AFR exome AF: 0.0590

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.0989

Gnomad4 FIN exome AF: 0.00609

Gnomad4 NFE exome AF: 0.00442

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0973 AC: 10853 AN: 111546 Hom.: 165 Cov.: 31 AF XY: 0.104 AC XY: 5626 AN XY: 54138

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0394

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.0557

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.105 Hom.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	16
DANN	Benign	0.12

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: rs4042056; hg19: chr14-106235614;