rs232230

Positions:

• chr2-88857435-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000390237.2(IGKC):​c.247G>C​(p.Val83Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 776,726 control chromosomes in the GnomAD database, including 9,166 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (3140 hom., cov: 32)
  • Exomes 𝑓: 0.11 (6026 hom.)
• Consequence: IGKC ENST00000390237.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.95

Genes affected

IGKC (HGNC:5716): (immunoglobulin kappa constant) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Involved in retina homeostasis. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

IGKC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGKC	unassigned_transcript_382	c.247G>C	p.Val83Leu	missense_variant	1/1
IGK		n.88857435C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGKC	ENST00000390237.2	c.247G>C	p.Val83Leu	missense_variant	1/1	6		ENSP00000374777.2
ENSG00000240040	ENST00000624935.3	n.39+4090G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25073 AN: 148942 Hom.: 3130 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.0984

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.161

GnomAD3 exomes AF: 0.135 AC: 33280 AN: 245870 Hom.: 3578 AF XY: 0.123 AC XY: 16463 AN XY: 133618

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.308

Gnomad SAS exome AF: 0.0662

Gnomad FIN exome AF: 0.0670

Gnomad NFE exome AF: 0.0811

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.111 AC: 69525 AN: 627700 Hom.: 6026 Cov.: 0 AF XY: 0.104 AC XY: 35465 AN XY: 341990

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.259

Gnomad4 ASJ exome AF: 0.0351

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.0659

Gnomad4 FIN exome AF: 0.0624

Gnomad4 NFE exome AF: 0.0811

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.169 AC: 25112 AN: 149026 Hom.: 3140 Cov.: 32 AF XY: 0.168 AC XY: 12183 AN XY: 72660

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0669

Gnomad4 NFE AF: 0.0829

Gnomad4 OTH AF: 0.164

Alfa AF: 0.0999 Hom.: 365

Bravo AF: 0.196

Asia WGS AF: 0.165 AC: 563 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs232230; hg19: chr2-89156948; COSMIC: COSV66419684;