rs34295723

chr14-105766769-G-Achr14-105766769-G-C

Variant summary

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

The ENST00000641136.1(IGHG3):c.1257-772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 139,360 control chromosomes in the GnomAD database, including 20,164 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 0.51 (20164 hom., cov: 22)
• Consequence: IGHG3 ENST00000641136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 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.1257-772C>T		intron_variant				P5

Frequencies

GnomAD3 genomes AF: 0.512 AC: 71247 AN: 139242 Hom.: 20169 Cov.: 22

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.511 AC: 71258 AN: 139360 Hom.: 20164 Cov.: 22 AF XY: 0.502 AC XY: 33914 AN XY: 67622

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.528

Alfa AF: 0.579 Hom.: 2800

Asia WGS AF: 0.305 AC: 1057 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.2
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34295723; hg19: chr14-106233106; COSMIC: COSV66653132;