14-105769274-A-T

Variant names:

• chr14-105769274-A-T
• rs1051112
• ENST00000641136.1:c.1094T>A

Variant summary

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

The ENST00000641136.1(IGHG3):​c.1094T>A​(p.Phe365Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 757,316 control chromosomes in the GnomAD database, including 57,198 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 0.34 (7624 hom., cov: 30)
  • Exomes 𝑓: 0.36 (49574 hom.)
• Consequence: IGHG3 ENST00000641136.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 6 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.517 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG3	ENST00000641136.1		c.1094T>A	p.Phe365Tyr	missense	Exon 7 of 9	ENSP00000492969.1
	IGHG3	ENST00000390551.6	TSL:6	c.1094T>A	p.Phe365Tyr	missense	Exon 7 of 7	ENSP00000374993.2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 44782 AN: 132500 Hom.: 7602 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.416 AC: 92368 AN: 221858 AF XY: 0.409

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.657

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.363 AC: 226477 AN: 624748 Hom.: 49574 Cov.: 0 AF XY: 0.358 AC XY: 121963 AN XY: 340462

African (AFR) AF: 0.129 AC: 2156 AN: 16758

American (AMR) AF: 0.628 AC: 27356 AN: 43582

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 4511 AN: 20836

East Asian (EAS) AF: 0.722 AC: 26010 AN: 36024

South Asian (SAS) AF: 0.429 AC: 29675 AN: 69170

European-Finnish (FIN) AF: 0.405 AC: 21509 AN: 53088

Middle Eastern (MID) AF: 0.253 AC: 887 AN: 3504

European-Non Finnish (NFE) AF: 0.297 AC: 103838 AN: 349068

Other (OTH) AF: 0.322 AC: 10535 AN: 32718

GnomAD4 genome AF: 0.338 AC: 44831 AN: 132568 Hom.: 7624 Cov.: 30 AF XY: 0.355 AC XY: 22987 AN XY: 64804

African (AFR) AF: 0.241 AC: 6949 AN: 28786

American (AMR) AF: 0.527 AC: 7398 AN: 14032

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 751 AN: 3270

East Asian (EAS) AF: 0.500 AC: 2245 AN: 4494

South Asian (SAS) AF: 0.479 AC: 2054 AN: 4286

European-Finnish (FIN) AF: 0.432 AC: 4373 AN: 10126

Middle Eastern (MID) AF: 0.293 AC: 54 AN: 184

European-Non Finnish (NFE) AF: 0.312 AC: 20165 AN: 64664

Other (OTH) AF: 0.330 AC: 618 AN: 1870

Alfa AF: 0.202 Hom.: 569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	5.9
DANN	Benign	0.45
PhyloP100		-0.035
Mutation Taster		=8/92	disease causing

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

Other links and lift over

dbSNP: rs1051112; hg19: chr14-106235611;