chr6-35312920-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000316637.7(DEF6):​c.807+148C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEF6 ENST00000316637.7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316637.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEF6	ENST00000316637.7	TSL:1 MANE Select	c.807+148C>A		intron	N/A	ENSP00000319831.5
	DEF6	ENST00000444278.3	TSL:3	c.696+148C>A		intron	N/A	ENSP00000415357.3
	DEF6	ENST00000698929.1		n.423+2276C>A		intron	N/A	ENSP00000514040.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 736956 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 372530

African (AFR) AF: 0.00 AC: 0 AN: 17942

American (AMR) AF: 0.00 AC: 0 AN: 20470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15782

East Asian (EAS) AF: 0.00 AC: 0 AN: 32294

South Asian (SAS) AF: 0.00 AC: 0 AN: 51852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2572

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 527094

Other (OTH) AF: 0.00 AC: 0 AN: 35414

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.85
PhyloP100		0.0030

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;