chr14-105769317-T-C

Position:

• chr14-105769317-T-C

Variant summary

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

The ENST00000641136.1(IGHG3):​c.1054A>G​(p.Ile352Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 752,098 control chromosomes in the GnomAD database, including 679 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 0.057 (459 hom., cov: 31)
  • Exomes 𝑓: 0.0059 (220 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.34

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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHG3	ENST00000641136.1	c.1054A>G	p.Ile352Val	missense_variant	7/9			ENSP00000492969	P5
IGHG3	ENST00000390551.6	c.1054A>G	p.Ile352Val	missense_variant	7/7			ENSP00000374993	A2

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 7618 AN: 132870 Hom.: 454 Cov.: 31

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.00233

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.00215

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.00488

Gnomad MID AF: 0.0140

Gnomad NFE AF: 0.00540

Gnomad OTH AF: 0.0419

GnomAD3 exomes AF: 0.00848 AC: 2048 AN: 241418 Hom.: 161 AF XY: 0.00684 AC XY: 900 AN XY: 131532

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00651

Gnomad ASJ exome AF: 0.00233

Gnomad EAS exome AF: 0.000959

Gnomad SAS exome AF: 0.000863

Gnomad FIN exome AF: 0.000190

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00655

GnomAD4 exome AF: 0.00589 AC: 3644 AN: 619170 Hom.: 220 Cov.: 0 AF XY: 0.00477 AC XY: 1613 AN XY: 337858

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00753

Gnomad4 ASJ exome AF: 0.000336

Gnomad4 EAS exome AF: 0.000744

Gnomad4 SAS exome AF: 0.000864

Gnomad4 FIN exome AF: 0.000228

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0574 AC: 7634 AN: 132928 Hom.: 459 Cov.: 31 AF XY: 0.0561 AC XY: 3610 AN XY: 64352

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.00215

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.00488

Gnomad4 NFE AF: 0.00540

Gnomad4 OTH AF: 0.0433

Alfa AF: 0.0222 Hom.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0010
DANN	Benign	0.21

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: rs79545032; hg19: chr14-106235654;