NM_022047.4:c.807+148C>T

Variant names:

• chr6-35312920-C-T
• rs6938946
• NM_022047.4:c.807+148C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 87 and autoimmunity

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF6	NM_022047.4	MANE Select	c.807+148C>T		intron	N/A	NP_071330.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF6	ENST00000316637.7	TSL:1 MANE Select	c.807+148C>T		intron	N/A	ENSP00000319831.5
	DEF6	ENST00000852046.1		c.807+148C>T		intron	N/A	ENSP00000522105.1
	DEF6	ENST00000852042.1		c.807+148C>T		intron	N/A	ENSP00000522101.1

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

African (AFR) AF: 0.755 AC: 13535 AN: 17918

American (AMR) AF: 0.836 AC: 17105 AN: 20460

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 10519 AN: 15766

East Asian (EAS) AF: 0.670 AC: 21635 AN: 32268

South Asian (SAS) AF: 0.821 AC: 42531 AN: 51802

European-Finnish (FIN) AF: 0.863 AC: 28920 AN: 33526

Middle Eastern (MID) AF: 0.756 AC: 1944 AN: 2570

European-Non Finnish (NFE) AF: 0.845 AC: 444861 AN: 526408

Other (OTH) AF: 0.814 AC: 28822 AN: 35388

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

African (AFR) AF: 0.757 AC: 31384 AN: 41440

American (AMR) AF: 0.844 AC: 12911 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2321 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3526 AN: 5168

South Asian (SAS) AF: 0.816 AC: 3935 AN: 4820

European-Finnish (FIN) AF: 0.857 AC: 9069 AN: 10588

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57760 AN: 67996

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.837 Hom.: 27365

Bravo AF: 0.804

Asia WGS AF: 0.728 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.9
DANN	Benign	0.84
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6938946; hg19: chr6-35280697;