rs60746425

Variant names:

• chr14-105769804-G-A
• rs60746425
• ENST00000641136.1:c.661C>T
• IGHG3 p.Arg221Trp

Your query was ambiguous. Multiple possible variants found:

• chr14-105769804-G-A
• chr14-105769804-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000641136.1(IGHG3):​c.661C>T​(p.Arg221Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 777,922 control chromosomes in the GnomAD database, including 1,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 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 0.0083 (69 hom., cov: 32)
  • Exomes 𝑓: 0.025 (1146 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0851 is higher than 0.05.

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>T	p.Arg221Trp	missense	Exon 6 of 9	ENSP00000492969.1	A0A9H4DHQ2
	IGHG3	ENST00000390551.6	TSL:6	c.661C>T	p.Arg221Trp	missense	Exon 6 of 7	ENSP00000374993.2	A0A9H3ZR93

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1252 AN: 150360 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.00108

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00835

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0653

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0233

Gnomad NFE AF: 0.00299

Gnomad OTH AF: 0.0136

GnomAD2 exomes AF: 0.0201 AC: 4962 AN: 246430 AF XY: 0.0227

Gnomad AFR exome AF: 0.00110

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.0650

Gnomad FIN exome AF: 0.00436

Gnomad NFE exome AF: 0.00385

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.0246 AC: 15432 AN: 627480 Hom.: 1146 Cov.: 0 AF XY: 0.0273 AC XY: 9325 AN XY: 341872

African (AFR) AF: 0.00125 AC: 22 AN: 17658

American (AMR) AF: 0.0170 AC: 742 AN: 43702

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 354 AN: 20914

East Asian (EAS) AF: 0.184 AC: 6639 AN: 36064

South Asian (SAS) AF: 0.0820 AC: 5720 AN: 69752

European-Finnish (FIN) AF: 0.00405 AC: 215 AN: 53126

Middle Eastern (MID) AF: 0.0290 AC: 104 AN: 3590

European-Non Finnish (NFE) AF: 0.00345 AC: 1206 AN: 349702

Other (OTH) AF: 0.0130 AC: 430 AN: 32972

GnomAD4 genome AF: 0.00828 AC: 1246 AN: 150442 Hom.: 69 Cov.: 32 AF XY: 0.0101 AC XY: 738 AN XY: 73378

African (AFR) AF: 0.00107 AC: 44 AN: 40974

American (AMR) AF: 0.00821 AC: 122 AN: 14856

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.0922 AC: 447 AN: 4850

South Asian (SAS) AF: 0.0651 AC: 301 AN: 4626

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10614

Middle Eastern (MID) AF: 0.0246 AC: 6 AN: 244

European-Non Finnish (NFE) AF: 0.00298 AC: 202 AN: 67816

Other (OTH) AF: 0.0125 AC: 26 AN: 2082

Alfa AF: 0.00593 Hom.: 1

Bravo AF: 0.00729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		-0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;