rs1042248

Variant names:

• chr14-105742188-G-C
• rs1042248
• ENST00000390548.6:c.375C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The ENST00000390548.6(IGHG1):​c.375C>G​(p.Leu125Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000872 in 780,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000097 (1 hom.)
• Consequence: IGHG1 ENST00000390548.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=2.31 with no splicing effect.

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.375C>G	p.Leu125Leu	synonymous	Exon 3 of 6	ENSP00000374990.2
	IGHG1	ENST00000390549.6	TSL:6	c.375C>G	p.Leu125Leu	synonymous	Exon 3 of 4	ENSP00000374991.2
	IGHG1	ENST00000390542.6	TSL:6	c.375C>G	p.Leu125Leu	synonymous	Exon 3 of 5	ENSP00000374984.2

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151850 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000211 AC: 52 AN: 246174 AF XY: 0.000194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000971 AC: 61 AN: 628120 Hom.: 1 Cov.: 0 AF XY: 0.0000994 AC XY: 34 AN XY: 342184

African (AFR) AF: 0.00 AC: 0 AN: 17686

American (AMR) AF: 0.00114 AC: 50 AN: 43726

Ashkenazi Jewish (ASJ) AF: 0.0000477 AC: 1 AN: 20958

East Asian (EAS) AF: 0.00 AC: 0 AN: 36068

South Asian (SAS) AF: 0.0000287 AC: 2 AN: 69784

European-Finnish (FIN) AF: 0.0000566 AC: 3 AN: 53020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.0000114 AC: 4 AN: 349696

Other (OTH) AF: 0.0000303 AC: 1 AN: 33048

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151968 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.000262 AC: 4 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000301 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		2.3
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1042248; hg19: chr14-106208525;