22-22822846-C-G

Variant names:

• chr22-22822846-C-G
• rs5996397
• ENST00000620395.2:c.26C>G

Variant summary

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

The ENST00000620395.2(IGLV2-8):​c.26C>G​(p.Thr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 775,518 control chromosomes in the GnomAD database, including 11,752 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 0.20 (3708 hom., cov: 31)
  • Exomes 𝑓: 0.15 (8044 hom.)
• Consequence: IGLV2-8 ENST00000620395.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 5 publications found

Genes affected

IGLV2-8 (HGNC:5895): (immunoglobulin lambda variable 2-8) 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]

MIR650 (HGNC:32906): (microRNA 650) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

IGL (HGNC:5853):

LOC105372948 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000620395.2. 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
	MIR650	NR_030755.1		n.71C>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGLV2-8	ENST00000620395.2	TSL:6	c.26C>G	p.Thr9Ser	missense	Exon 1 of 2	ENSP00000482937.2	P01709
	MIR650	ENST00000385101.1	TSL:6	n.71C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30302 AN: 150362 Hom.: 3706 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.0801

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.150 AC: 35954 AN: 239910 AF XY: 0.145

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.000558

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.150 AC: 93554 AN: 625052 Hom.: 8044 Cov.: 0 AF XY: 0.146 AC XY: 49819 AN XY: 340540

African (AFR) AF: 0.329 AC: 5666 AN: 17222

American (AMR) AF: 0.149 AC: 6402 AN: 43006

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3096 AN: 20722

East Asian (EAS) AF: 0.000250 AC: 9 AN: 36040

South Asian (SAS) AF: 0.0923 AC: 6426 AN: 69584

European-Finnish (FIN) AF: 0.153 AC: 8109 AN: 53016

Middle Eastern (MID) AF: 0.129 AC: 524 AN: 4060

European-Non Finnish (NFE) AF: 0.167 AC: 58272 AN: 348482

Other (OTH) AF: 0.153 AC: 5050 AN: 32920

GnomAD4 genome AF: 0.202 AC: 30333 AN: 150466 Hom.: 3708 Cov.: 31 AF XY: 0.197 AC XY: 14469 AN XY: 73558

African (AFR) AF: 0.325 AC: 13183 AN: 40502

American (AMR) AF: 0.179 AC: 2707 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 546 AN: 3460

East Asian (EAS) AF: 0.000809 AC: 4 AN: 4946

South Asian (SAS) AF: 0.0808 AC: 385 AN: 4766

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10598

Middle Eastern (MID) AF: 0.154 AC: 41 AN: 266

European-Non Finnish (NFE) AF: 0.166 AC: 11231 AN: 67836

Other (OTH) AF: 0.174 AC: 363 AN: 2088

Alfa AF: 0.138 Hom.: 546

Bravo AF: 0.210

Asia WGS AF: 0.0530 AC: 186 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.79
DANN	Benign	0.60
PhyloP100		-1.1

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: rs5996397; hg19: chr22-23165340;