6-35312920-C-T

Position:

• chr6-35312920-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022047.4(DEF6):​c.807+148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 888,204 control chromosomes in the GnomAD database, including 304,669 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50480 hom., cov: 30)
  • Exomes 𝑓: 0.83 (254189 hom.)
• Consequence: DEF6 NM_022047.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEF6	NM_022047.4	c.807+148C>T		intron_variant		ENST00000316637.7	NP_071330.3
DEF6	XM_047418838.1	c.477+148C>T		intron_variant			XP_047274794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEF6	ENST00000316637.7	c.807+148C>T		intron_variant		1	NM_022047.4	ENSP00000319831	P1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123444 AN: 151980 Hom.: 50435 Cov.: 30

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.829 AC: 609872 AN: 736106 Hom.: 254189 AF XY: 0.828 AC XY: 308197 AN XY: 372114

Gnomad4 AFR exome AF: 0.755

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.670

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.863

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.814

GnomAD4 genome AF: 0.812 AC: 123542 AN: 152098 Hom.: 50480 Cov.: 30 AF XY: 0.811 AC XY: 60325 AN XY: 74350

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.799

Alfa AF: 0.838 Hom.: 24385

Bravo AF: 0.804

Asia WGS AF: 0.728 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.9
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs6938946; hg19: chr6-35280697;