rs12897751

chr14-105767411-G-C

Variant summary

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

The ENST00000641136.1(IGHG3):c.1256+402C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 128,782 control chromosomes in the GnomAD database, including 16,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (16205 hom., cov: 19)
• Consequence: IGHG3 ENST00000641136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.65

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 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.1256+402C>G		intron_variant				P5

Frequencies

GnomAD3 genomes AF: 0.440 AC: 56583 AN: 128662 Hom.: 16210 Cov.: 19

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.609

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.439 AC: 56574 AN: 128782 Hom.: 16205 Cov.: 19 AF XY: 0.429 AC XY: 26645 AN XY: 62136

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.478

Alfa AF: 0.520 Hom.: 2472

Asia WGS AF: 0.195 AC: 671 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.4
Dann	Benign	0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12897751; hg19: chr14-106233748;