22-22697977-T-C

Variant names:

• chr22-22697977-T-C
• rs1312
• ENST00000390306.2:c.27T>C

Variant summary

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

The ENST00000390306.2(IGLV2-23):​c.27T>C​(p.Thr9Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 775,160 control chromosomes in the GnomAD database, including 80,552 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 0.46 (16292 hom., cov: 31)
  • Exomes 𝑓: 0.45 (64260 hom.)
• Consequence: IGLV2-23 ENST00000390306.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 6 publications found

Genes affected

IGLV2-23 (HGNC:5890): (immunoglobulin lambda variable 2-23) Predicted to be involved in immune response. Predicted to be located in extracellular region and plasma membrane. Predicted to be part of immunoglobulin complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGL (HGNC:5853):

LL22NC03-102D1.18 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000390306.2. 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
	IGLV2-23	ENST00000390306.2	TSL:6	c.27T>C	p.Thr9Thr	synonymous	Exon 1 of 2	ENSP00000374841.2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 68761 AN: 150178 Hom.: 16280 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.467 AC: 110712 AN: 237308 AF XY: 0.464

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.584

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.488

Gnomad FIN exome AF: 0.465

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.448 AC: 280151 AN: 624870 Hom.: 64260 Cov.: 0 AF XY: 0.449 AC XY: 152825 AN XY: 340390

African (AFR) AF: 0.500 AC: 8781 AN: 17576

American (AMR) AF: 0.577 AC: 24719 AN: 42846

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 9887 AN: 20832

East Asian (EAS) AF: 0.500 AC: 17973 AN: 35972

South Asian (SAS) AF: 0.489 AC: 34017 AN: 69584

European-Finnish (FIN) AF: 0.459 AC: 24230 AN: 52788

Middle Eastern (MID) AF: 0.543 AC: 2247 AN: 4138

European-Non Finnish (NFE) AF: 0.412 AC: 143428 AN: 348196

Other (OTH) AF: 0.451 AC: 14869 AN: 32938

GnomAD4 genome AF: 0.458 AC: 68806 AN: 150290 Hom.: 16292 Cov.: 31 AF XY: 0.464 AC XY: 34067 AN XY: 73390

African (AFR) AF: 0.495 AC: 19966 AN: 40358

American (AMR) AF: 0.521 AC: 7894 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1643 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2429 AN: 4946

South Asian (SAS) AF: 0.500 AC: 2384 AN: 4764

European-Finnish (FIN) AF: 0.475 AC: 5010 AN: 10542

Middle Eastern (MID) AF: 0.479 AC: 134 AN: 280

European-Non Finnish (NFE) AF: 0.414 AC: 28091 AN: 67792

Other (OTH) AF: 0.468 AC: 979 AN: 2090

Alfa AF: 0.392 Hom.: 3364

Asia WGS AF: 0.482 AC: 1675 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.73
PhyloP100		-2.9

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: rs1312; hg19: chr22-23040462;