rs77307099

Variant names:

• chr14-105769430-C-T
• rs77307099
• ENST00000641136.1:c.938G>A
• IGHG3 p.Ser313Asn

Variant summary

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

The ENST00000641136.1(IGHG3):​c.938G>A​(p.Ser313Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 771,530 control chromosomes in the GnomAD database, including 47,818 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 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 0.27 (6564 hom., cov: 30)
  • Exomes 𝑓: 0.34 (41254 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 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.938G>A	p.Ser313Asn	missense	Exon 7 of 9	ENSP00000492969.1	A0A9H4DHQ2
	IGHG3	ENST00000390551.6	TSL:6	c.938G>A	p.Ser313Asn	missense	Exon 7 of 7	ENSP00000374993.2	A0A9H3ZR93

Frequencies

GnomAD3 genomes AF: 0.266 AC: 38983 AN: 146674 Hom.: 6554 Cov.: 30

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.272

GnomAD2 exomes AF: 0.337 AC: 77755 AN: 230666 AF XY: 0.327

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.335 AC: 209299 AN: 624770 Hom.: 41254 Cov.: 0 AF XY: 0.328 AC XY: 111737 AN XY: 340366

African (AFR) AF: 0.0759 AC: 1332 AN: 17540

American (AMR) AF: 0.607 AC: 26500 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 4156 AN: 20874

East Asian (EAS) AF: 0.537 AC: 19339 AN: 36002

South Asian (SAS) AF: 0.345 AC: 23979 AN: 69444

European-Finnish (FIN) AF: 0.401 AC: 21265 AN: 53080

Middle Eastern (MID) AF: 0.200 AC: 510 AN: 2544

European-Non Finnish (NFE) AF: 0.293 AC: 102293 AN: 348856

Other (OTH) AF: 0.303 AC: 9925 AN: 32794

GnomAD4 genome AF: 0.266 AC: 39002 AN: 146760 Hom.: 6564 Cov.: 30 AF XY: 0.279 AC XY: 19961 AN XY: 71496

African (AFR) AF: 0.0821 AC: 3168 AN: 38580

American (AMR) AF: 0.475 AC: 6904 AN: 14520

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 691 AN: 3460

East Asian (EAS) AF: 0.368 AC: 1714 AN: 4658

South Asian (SAS) AF: 0.372 AC: 1671 AN: 4490

European-Finnish (FIN) AF: 0.407 AC: 4264 AN: 10478

Middle Eastern (MID) AF: 0.195 AC: 46 AN: 236

European-Non Finnish (NFE) AF: 0.293 AC: 19771 AN: 67392

Other (OTH) AF: 0.270 AC: 551 AN: 2038

Alfa AF: 0.268 Hom.: 2657

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.011
DANN	Benign	0.27
PhyloP100		-0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs77307099;

hg19: chr14-106235767;