rs8009156

Variant names:

• chr14-105643800-C-T
• rs8009156
• ENST00000641095.1:c.481G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641095.1(IGHG2):​c.481G>A​(p.Val161Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 779,382 control chromosomes in the GnomAD database, including 68,607 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.

• Frequency:
  • Genomes: 𝑓 0.33 (10781 hom., cov: 34)
  • Exomes 𝑓: 0.41 (57826 hom.)
• Consequence: IGHG2 ENST00000641095.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 10 publications found

Genes affected

IGHG2 (HGNC:5526): (immunoglobulin heavy constant gamma 2 (G2m 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. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGHG2 Gene-Disease associations (from GenCC):

• recurrent infections associated with rare immunoglobulin isotypes deficiency

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641095.1. 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
	IGHG2	ENST00000641095.1		c.481G>A	p.Val161Met	missense	Exon 3 of 6	ENSP00000493129.1	P01859-2
	IGHG2	ENST00000390545.3	TSL:6	c.481G>A	p.Val161Met	missense	Exon 3 of 4	ENSP00000374987.2	P01859-1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50615 AN: 151422 Hom.: 10779 Cov.: 34

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.394 AC: 97225 AN: 246622 AF XY: 0.408

Gnomad AFR exome AF: 0.0760

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.604

Gnomad EAS exome AF: 0.536

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.409 AC: 256701 AN: 627842 Hom.: 57826 Cov.: 0 AF XY: 0.415 AC XY: 142090 AN XY: 342024

African (AFR) AF: 0.0788 AC: 1392 AN: 17674

American (AMR) AF: 0.223 AC: 9739 AN: 43708

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 12502 AN: 20976

East Asian (EAS) AF: 0.266 AC: 9578 AN: 36040

South Asian (SAS) AF: 0.380 AC: 26477 AN: 69708

European-Finnish (FIN) AF: 0.417 AC: 22144 AN: 53106

Middle Eastern (MID) AF: 0.512 AC: 2015 AN: 3932

European-Non Finnish (NFE) AF: 0.454 AC: 158736 AN: 349672

Other (OTH) AF: 0.427 AC: 14118 AN: 33026

GnomAD4 genome AF: 0.334 AC: 50600 AN: 151540 Hom.: 10781 Cov.: 34 AF XY: 0.333 AC XY: 24633 AN XY: 74038

African (AFR) AF: 0.0826 AC: 3420 AN: 41412

American (AMR) AF: 0.288 AC: 4385 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2111 AN: 3464

East Asian (EAS) AF: 0.482 AC: 2484 AN: 5152

South Asian (SAS) AF: 0.381 AC: 1815 AN: 4770

European-Finnish (FIN) AF: 0.418 AC: 4403 AN: 10522

Middle Eastern (MID) AF: 0.503 AC: 146 AN: 290

European-Non Finnish (NFE) AF: 0.452 AC: 30601 AN: 67724

Other (OTH) AF: 0.377 AC: 791 AN: 2098

Alfa AF: 0.408 Hom.: 6073

Bravo AF: 0.314

Asia WGS AF: 0.437 AC: 1518 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.20
DANN	Benign	0.97
PhyloP100		-3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8009156; hg19: chr14-106110137; COSMIC: COSV66640482;