ENST00000641136.1:c.661C>T

Variant names:

• chr14-105769806-G-A
• rs74093865
• ENST00000641136.1:c.659C>T
• IGHG3 p.Pro220Leu

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641136.1(IGHG3):​c.659C>T​(p.Pro220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 777,512 control chromosomes in the GnomAD database, including 47,896 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 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 0.26 (6740 hom., cov: 32)
  • Exomes 𝑓: 0.33 (41156 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.468 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.659C>T	p.Pro220Leu	missense	Exon 6 of 9	ENSP00000492969.1	A0A9H4DHQ2
	IGHG3	ENST00000390551.6	TSL:6	c.659C>T	p.Pro220Leu	missense	Exon 6 of 7	ENSP00000374993.2	A0A9H3ZR93

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39198 AN: 150060 Hom.: 6728 Cov.: 32

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.269

GnomAD2 exomes AF: 0.351 AC: 86454 AN: 246288 AF XY: 0.342

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.362

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.335 AC: 210007 AN: 627362 Hom.: 41156 Cov.: 0 AF XY: 0.328 AC XY: 112273 AN XY: 341834

African (AFR) AF: 0.0679 AC: 1199 AN: 17660

American (AMR) AF: 0.605 AC: 26440 AN: 43684

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4175 AN: 20894

East Asian (EAS) AF: 0.534 AC: 19240 AN: 36062

South Asian (SAS) AF: 0.347 AC: 24220 AN: 69750

European-Finnish (FIN) AF: 0.401 AC: 21302 AN: 53124

Middle Eastern (MID) AF: 0.224 AC: 811 AN: 3616

European-Non Finnish (NFE) AF: 0.294 AC: 102659 AN: 349606

Other (OTH) AF: 0.302 AC: 9961 AN: 32966

GnomAD4 genome AF: 0.261 AC: 39221 AN: 150150 Hom.: 6740 Cov.: 32 AF XY: 0.275 AC XY: 20127 AN XY: 73208

African (AFR) AF: 0.0696 AC: 2848 AN: 40936

American (AMR) AF: 0.477 AC: 7051 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 695 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1765 AN: 4802

South Asian (SAS) AF: 0.378 AC: 1739 AN: 4606

European-Finnish (FIN) AF: 0.410 AC: 4339 AN: 10594

Middle Eastern (MID) AF: 0.215 AC: 52 AN: 242

European-Non Finnish (NFE) AF: 0.295 AC: 19951 AN: 67726

Other (OTH) AF: 0.269 AC: 558 AN: 2078

Alfa AF: 0.277 Hom.: 2101

Bravo AF: 0.262

Asia WGS AF: 0.346 AC: 1193 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.73
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74093865;

hg19: chr14-106236143;