Variant 22-22822846-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Variant links:

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]

IGLV2-8 links:

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]

MIR650 links:

LOC105372948 (HGNC:):

LOC105372948 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons
MIR650	NR_030755.1 linkuse as main transcript	n.71C>G	non_coding_transcript_exon_variant	1/1
LOC105372948	XR_938047.2 linkuse as main transcript	n.906-1210G>C	intron_variant, non_coding_transcript_variant
LOC105372948	XR_001755438.2 linkuse as main transcript	n.353-1210G>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGLV2-8	ENST00000620395.2 linkuse as main transcript	c.26C>G	p.Thr9Ser	missense_variant	1/2			ENSP00000482937	P1
MIR650	ENST00000385101.1 linkuse as main transcript	n.71C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30302

AN:

150362

Hom.:

3706

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.150

AC:

35954

AN:

239910

Hom.:

3237

AF XY:

0.145

AC XY:

18964

AN XY:

130408

show subpopulations

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 SAS exome

AF:

0.0897

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.:

AF XY:

0.146

AC XY:

49819

AN XY:

340540

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.000250

Gnomad4 SAS exome

AF:

0.0923

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.202

AC:

30333

AN:

150466

Hom.:

3708

Cov.:

AF XY:

0.197

AC XY:

14469

AN XY:

73558

show subpopulations

Gnomad4 AFR

AF:

0.325

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.000809

Gnomad4 SAS

AF:

0.0808

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.174

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.79

DANN

Benign

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over