Variant 14-105741745-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000390548.6(IGHG1):c.721C>A(p.Leu241Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 734,134 control chromosomes in the GnomAD database, including 137,999 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 ( 21452 hom., cov: 26)

Exomes 𝑓: 0.57 ( 116547 hom. )

Consequence

IGHG1
ENST00000390548.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Variant links:

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 links:

IGHG1 (HGNC:):

IGHG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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	Protein	UniProt
IGHG1	unassigned_transcript_2475 use as main transcript	c.718C>A	p.Leu240Met	missense_variant	4/4
IGH	use as main transcript	n.105741745G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
IGHG1	ENST00000390548.6 linkuse as main transcript	c.721C>A	p.Leu241Met	missense_variant	4/6	6	ENSP00000374990.2	P01857-2
IGHG1	ENST00000390549.6 linkuse as main transcript	c.721C>A	p.Leu241Met	missense_variant	4/4	6	ENSP00000374991.2	P01857-1
IGHG1	ENST00000390542.6 linkuse as main transcript	c.616C>A	p.Leu206Met	missense_variant	5/5	6	ENSP00000374984.2	A0A0A0MS07

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

69633

AN:

148088

Hom.:

21459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.406

Gnomad ASJ

AF:

0.774

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.694

Gnomad OTH

AF:

0.509

GnomAD3 exomes

AF:

0.365

AC:

67341

AN:

184476

Hom.:

24468

AF XY:

0.378

AC XY:

36776

AN XY:

97410

show subpopulations

Gnomad AFR exome

AF:

0.0590

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.00647

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.590

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.575

AC:

336842

AN:

585916

Hom.:

116547

Cov.:

AF XY:

0.585

AC XY:

185459

AN XY:

316978

show subpopulations

Gnomad4 AFR exome

AF:

0.0991

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.00775

Gnomad4 SAS exome

AF:

0.494

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.470

AC:

69611

AN:

148218

Hom.:

21452

Cov.:

AF XY:

0.458

AC XY:

33037

AN XY:

72074

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.774

Gnomad4 EAS

AF:

0.0169

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.581

Gnomad4 NFE

AF:

0.694

Gnomad4 OTH

AF:

0.503

Alfa

AF:

0.483

Hom.:

4257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.91

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over