chr14-105769804-G-T

Variant names:

• chr14-105769804-G-T
• rs60746425
• ENST00000641136.1:c.661C>A
• IGHG3 p.Arg221Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000641136.1(IGHG3):​c.661C>A​(p.Arg221Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 627,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: IGHG3 ENST00000641136.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 0 publications found

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]

IGH (HGNC:5477):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-0.756 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641136.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG3	ENST00000641136.1		c.661C>A	p.Arg221Arg	synonymous	Exon 6 of 9	ENSP00000492969.1	A0A9H4DHQ2
	IGHG3	ENST00000390551.6	TSL:6	c.661C>A	p.Arg221Arg	synonymous	Exon 6 of 7	ENSP00000374993.2	A0A9H3ZR93

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 1 AN: 627480 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 341872

African (AFR) AF: 0.00 AC: 0 AN: 17658

American (AMR) AF: 0.00 AC: 0 AN: 43702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20914

East Asian (EAS) AF: 0.00 AC: 0 AN: 36064

South Asian (SAS) AF: 0.00 AC: 0 AN: 69752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3590

European-Non Finnish (NFE) AF: 0.00000286 AC: 1 AN: 349702

Other (OTH) AF: 0.00 AC: 0 AN: 32972

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs60746425;

hg19: chr14-106236141;