Genetic Variant IGKV3D-15:p.Thr40Thr (chr2-90115175-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000417279.3(IGKV3D-15):c.120C>A(p.Thr40Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 7 hom., cov: 8)

Exomes 𝑓: 0.0017 ( 131 hom. )

Failed GnomAD Quality Control

Consequence

IGKV3D-15
ENST00000417279.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.299

Variant links:

Genes affected

IGKV3D-15 (HGNC:5824): (immunoglobulin kappa variable 3D-15) Predicted to be involved in immune response. Predicted to be located in plasma membrane. Predicted to be part of immunoglobulin complex. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

IGKV3D-15 links:

IGK (HGNC:5715):

IGK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 2-90115175-C-A is Benign according to our data. Variant chr2-90115175-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651111.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.299 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGKV3D-15	unassigned_transcript_454	c.120C>A	p.Thr40Thr	synonymous_variant	Exon 2 of 2
IGK		n.90115175C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGKV3D-15	ENST00000417279.3 link	c.120C>A	p.Thr40Thr	synonymous_variant	Exon 2 of 2	6		ENSP00000403672.3		A0A087WSY6

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

AN:

68412

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

Gnomad ASJ

AF:

0.00253

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000856

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000949

AC:

AN:

74818

Hom.:

AF XY:

0.000949

AC XY:

AN XY:

36874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000624

Gnomad ASJ exome

AF:

0.000513

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000777

Gnomad NFE exome

AF:

0.00193

Gnomad OTH exome

AF:

0.000455

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00171

AC:

834

AN:

486936

Hom.:

131

Cov.:

AF XY:

0.00179

AC XY:

465

AN XY:

259894

show subpopulations

Gnomad4 AFR exome

AF:

0.0000646

Gnomad4 AMR exome

AF:

0.000706

Gnomad4 ASJ exome

AF:

0.00116

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000393

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00187

GnomAD4 genome

AF:

0.00115

AC:

AN:

68404

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

30842

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000194

Gnomad4 ASJ

AF:

0.00253

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000856

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00195

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IGKV2D-28: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.9

DANN

Benign

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over