Variant chr6-35297934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_022047.4(DEF6):c.78C>T(p.Val26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,603,244 control chromosomes in the GnomAD database, including 1,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 597 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 621 hom. )

Consequence

DEF6
NM_022047.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.741

Variant links:

Genes affected

DEF6 (HGNC:2760): (DEF6 guanine nucleotide exchange factor) DEF6, or IBP, is a guanine nucleotide exchange factor (GEF) for RAC (MIM 602048) and CDC42 (MIM 116952) that is highly expressed in B and T cells (Gupta et al., 2003 [PubMed 12923183]).[supplied by OMIM, Mar 2008]

DEF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 6-35297934-C-T is Benign according to our data. Variant chr6-35297934-C-T is described in ClinVar as [Benign]. Clinvar id is 1170593.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.741 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEF6	NM_022047.4 linkuse as main transcript	c.78C>T	p.Val26=	synonymous_variant	1/11	ENST00000316637.7	NP_071330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEF6	ENST00000316637.7 linkuse as main transcript	c.78C>T	p.Val26=	synonymous_variant	1/11	1	NM_022047.4	ENSP00000319831	P1

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7558

AN:

152200

Hom.:

595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.0482

GnomAD3 exomes

AF:

0.0137

AC:

3137

AN:

229662

Hom.:

193

AF XY:

0.0105

AC XY:

1300

AN XY:

123960

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.00147

Gnomad EAS exome

AF:

0.0000587

Gnomad SAS exome

AF:

0.00100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00640

AC:

9280

AN:

1450926

Hom.:

621

Cov.:

AF XY:

0.00562

AC XY:

4052

AN XY:

720552

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.0163

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.00140

Gnomad4 FIN exome

AF:

0.0000577

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0498

AC:

7586

AN:

152318

Hom.:

597

Cov.:

AF XY:

0.0487

AC XY:

3629

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.0477

Alfa

AF:

0.0142

Hom.:

112

Bravo

AF:

0.0593

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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