IGHG1 p.Leu125Leu

Variant names:

• chr14-105742187-A-A
• ENST00000390548.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr14-105742188--
• chr14-105742188-G-A
• chr14-105742188-G-T
• chr14-105742188-G-C
• chr14-105742188-GAG-TAA
• chr14-105742188-GAG-CAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000390548.6(IGHG1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGHG1 ENST00000390548.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG1	ENST00000390548.6	TSL:6	c.		exon_region	Exon 3 of 6	ENSP00000374990.2	P01857-2
	IGHG1	ENST00000390549.6	TSL:6	c.		exon_region	Exon 3 of 4	ENSP00000374991.2	P01857-1
	IGHG1	ENST00000390542.6	TSL:6	c.		exon_region	Exon 3 of 5	ENSP00000374984.2	A0A0A0MS07

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-106208524;