Variant 14-106422120-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000390619.2(IGHV4-39):c.49C>G(p.Leu17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 823,474 control chromosomes in the GnomAD database, including 495 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 74 hom., cov: 27)

Exomes 𝑓: 0.0047 ( 421 hom. )

Consequence

IGHV4-39
ENST00000390619.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.139

Variant links:

Genes affected

IGHV4-39 (HGNC:5651): (immunoglobulin heavy variable 4-39) 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. Predicted to be located in extracellular region and plasma membrane. Predicted to be part of immunoglobulin complex, circulating. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IGHV4-39 links:

LOC124903400 (HGNC:):

LOC124903400 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 14-106422120-G-C is Benign according to our data. Variant chr14-106422120-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644932.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 74 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903400	XR_007064371.1 linkuse as main transcript	n.178+20418G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHV4-39	ENST00000390619.2 linkuse as main transcript	c.49C>G	p.Leu17Val	missense_variant	1/2			P1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

557

AN:

144486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00706

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000442

Gnomad MID

AF:

0.0133

Gnomad NFE

AF:

0.00665

Gnomad OTH

AF:

0.00306

GnomAD3 exomes

AF:

0.00340

AC:

832

AN:

244858

Hom.:

AF XY:

0.00338

AC XY:

450

AN XY:

133022

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00601

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.000991

Gnomad NFE exome

AF:

0.00562

Gnomad OTH exome

AF:

0.00450

GnomAD4 exome

AF:

0.00466

AC:

3165

AN:

678878

Hom.:

421

Cov.:

AF XY:

0.00459

AC XY:

1677

AN XY:

365688

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00590

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000339

Gnomad4 FIN exome

AF:

0.00162

Gnomad4 NFE exome

AF:

0.00650

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00385

AC:

557

AN:

144596

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

247

AN XY:

70256

show subpopulations

Gnomad4 AFR

AF:

0.000773

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00706

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000442

Gnomad4 NFE

AF:

0.00665

Gnomad4 OTH

AF:

0.00252

Alfa

AF:

0.00512

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

LINC00221: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

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