rs1045853

Positions:

• chr14-105741749-A-C
• chr14-105741749-A-G
• chr14-105741749-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000390548.6(IGHG1):​c.717T>G​(p.Asp239Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 733,814 control chromosomes in the GnomAD database, including 138,915 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (21508 hom., cov: 26)
  • Exomes 𝑓: 0.58 (117407 hom.)
• Consequence: IGHG1 ENST00000390548.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.34

Genes affected

IGHG1 (HGNC:5525): (immunoglobulin heavy constant gamma 1 (G1m marker)) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Predicted to be involved in several processes, including activation of immune response; defense response to other organism; and phagocytosis. Predicted to act upstream of or within several processes, including immunoglobulin mediated immune response; positive regulation of hypersensitivity; and positive regulation of phagocytosis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHG1	ENST00000390548.6	c.717T>G	p.Asp239Glu	missense_variant	4/6			P5
IGHG1	ENST00000390549.6	c.717T>G	p.Asp239Glu	missense_variant	4/4			A2
IGHG1	ENST00000390542.6	c.612T>G	p.Asp204Glu	missense_variant	5/5			A2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 69790 AN: 148086 Hom.: 21515 Cov.: 26

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.509

GnomAD3 exomes AF: 0.388 AC: 72245 AN: 186100 Hom.: 26311 AF XY: 0.403 AC XY: 39672 AN XY: 98500

Gnomad AFR exome AF: 0.0627

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.543

Gnomad EAS exome AF: 0.00658

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.612

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.578 AC: 338721 AN: 585600 Hom.: 117407 Cov.: 0 AF XY: 0.589 AC XY: 186586 AN XY: 317000

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.00789

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.471 AC: 69767 AN: 148214 Hom.: 21508 Cov.: 26 AF XY: 0.459 AC XY: 33133 AN XY: 72130

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.503

Alfa AF: 0.403 Hom.: 4678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0020
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1045853; hg19: chr14-106208086;