14-105742782-T-C

Variant names:

• chr14-105742782-T-C
• rs1071803
• ENST00000390548.6:c.290A>G

Variant summary

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

The ENST00000390548.6(IGHG1):​c.290A>G​(p.Lys97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 776,740 control chromosomes in the GnomAD database, including 148,059 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 0.49 (23257 hom., cov: 32)
  • Exomes 𝑓: 0.60 (124802 hom.)
• Consequence: IGHG1 ENST00000390548.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 13 publications found

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]

IGHG1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390548.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG1	ENST00000390548.6	TSL:6	c.290A>G	p.Lys97Arg	missense	Exon 1 of 6	ENSP00000374990.2
	IGHG1	ENST00000390549.6	TSL:6	c.290A>G	p.Lys97Arg	missense	Exon 1 of 4	ENSP00000374991.2
	IGHG1	ENST00000390542.6	TSL:6	c.290A>G	p.Lys97Arg	missense	Exon 1 of 5	ENSP00000374984.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74693 AN: 151434 Hom.: 23259 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.663

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.542

GnomAD2 exomes AF: 0.565 AC: 137267 AN: 243152 AF XY: 0.585

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.566

Gnomad FIN exome AF: 0.583

Gnomad NFE exome AF: 0.691

Gnomad OTH exome AF: 0.607

GnomAD4 exome AF: 0.605 AC: 377975 AN: 625188 Hom.: 124802 Cov.: 0 AF XY: 0.615 AC XY: 209324 AN XY: 340574

African (AFR) AF: 0.123 AC: 2168 AN: 17618

American (AMR) AF: 0.321 AC: 14012 AN: 43664

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 16214 AN: 20886

East Asian (EAS) AF: 0.277 AC: 9972 AN: 35994

South Asian (SAS) AF: 0.561 AC: 38973 AN: 69414

European-Finnish (FIN) AF: 0.595 AC: 31580 AN: 53066

Middle Eastern (MID) AF: 0.676 AC: 1697 AN: 2512

European-Non Finnish (NFE) AF: 0.697 AC: 243241 AN: 349198

Other (OTH) AF: 0.613 AC: 20118 AN: 32836

GnomAD4 genome AF: 0.493 AC: 74673 AN: 151552 Hom.: 23257 Cov.: 32 AF XY: 0.485 AC XY: 35902 AN XY: 73994

African (AFR) AF: 0.123 AC: 5108 AN: 41378

American (AMR) AF: 0.414 AC: 6276 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2598 AN: 5062

South Asian (SAS) AF: 0.541 AC: 2578 AN: 4764

European-Finnish (FIN) AF: 0.585 AC: 6186 AN: 10572

Middle Eastern (MID) AF: 0.648 AC: 184 AN: 284

European-Non Finnish (NFE) AF: 0.696 AC: 47218 AN: 67852

Other (OTH) AF: 0.547 AC: 1149 AN: 2102

Alfa AF: 0.629 Hom.: 8879

Bravo AF: 0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.68
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1071803; hg19: chr14-106209119;