chr14-105766248-A-G

Position:

• chr14-105766248-A-G

Variant summary

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

The ENST00000641136.1(IGHG3):​c.1257-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 142,862 control chromosomes in the GnomAD database, including 21,905 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 0.49 (21905 hom., cov: 32)
• Consequence: IGHG3 ENST00000641136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 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.1257-251T>C		intron_variant				P5

Frequencies

GnomAD3 genomes AF: 0.491 AC: 70067 AN: 142764 Hom.: 21913 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.490 AC: 70050 AN: 142862 Hom.: 21905 Cov.: 32 AF XY: 0.479 AC XY: 33378 AN XY: 69662

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.517

Alfa AF: 0.546 Hom.: 2282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10136766; hg19: chr14-106232585; COSMIC: COSV66652363;