rs77307099

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHG3	unassigned_transcript_2476	c.938G>A	p.Ser313Asn	missense_variant	Exon 7 of 9
IGHG3	unassigned_transcript_2477	c.938G>A	p.Ser313Asn	missense_variant	Exon 7 of 7
IGH		n.105769430C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHG3	ENST00000641136.1	c.938G>A	p.Ser313Asn	missense_variant	Exon 7 of 9			ENSP00000492969.1
IGHG3	ENST00000390551.6	c.938G>A	p.Ser313Asn	missense_variant	Exon 7 of 7	6		ENSP00000374993.2

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

GnomAD3 exomes AF: 0.337 AC: 77755 AN: 230666 Hom.: 17602 AF XY: 0.327 AC XY: 40962 AN XY: 125140

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 SAS exome AF: 0.367

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

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.303

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

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.270

Alfa AF: 0.268 Hom.: 2657

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs77307099; hg19: chr14-106235767;