14-105741745-G-C

Position:

• chr14-105741745-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000390548.6(IGHG1):​c.721C>G​(p.Leu241Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000162 in 617,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L241M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: IGHG1 ENST00000390548.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHG1	unassigned_transcript_2475	c.718C>G	p.Leu240Val	missense_variant	4/4
IGH		n.105741745G>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHG1	ENST00000390548.6	c.721C>G	p.Leu241Val	missense_variant	4/6	6		ENSP00000374990.2
IGHG1	ENST00000390549.6	c.721C>G	p.Leu241Val	missense_variant	4/4	6		ENSP00000374991.2
IGHG1	ENST00000390542.6	c.616C>G	p.Leu206Val	missense_variant	5/5	6		ENSP00000374984.2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000162 AC: 1 AN: 617700 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 336278

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000289

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11621259; hg19: chr14-106208082;