14-105742782-T-C

Position:

• chr14-105742782-T-C

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHG1	unassigned_transcript_2475	c.287A>G	p.Lys96Arg	missense_variant	1/4
IGH		n.105742782T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHG1	ENST00000390548.6	c.290A>G	p.Lys97Arg	missense_variant	1/6	6		ENSP00000374990.2
IGHG1	ENST00000390549.6	c.290A>G	p.Lys97Arg	missense_variant	1/4	6		ENSP00000374991.2
IGHG1	ENST00000390542.6	c.290A>G	p.Lys97Arg	missense_variant	1/5	6		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

GnomAD3 exomes AF: 0.565 AC: 137267 AN: 243152 Hom.: 44122 AF XY: 0.585 AC XY: 77218 AN XY: 131892

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 SAS exome AF: 0.537

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

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.595

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.613

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.547

Alfa AF: 0.629 Hom.: 8879

Bravo AF: 0.461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1071803; hg19: chr14-106209119;