rs934542

Positions:

• chr15-65723838-A-G

Variant summary

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

The NM_001320835.1(DENND4A):​c.1488-890T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,150 control chromosomes in the GnomAD database, including 50,039 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 (50039 hom., cov: 31)
• Consequence: DENND4A NM_001320835.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

DENND4A (HGNC:24321): (DENN domain containing 4A) This gene encodes a DENN domain-containing protein that may function as a guanine nucleotide exchange factor that specifically activates ras-related protein Rab-10. This protein also contains a interferon stimulated response element-binding domain and may be involved in regulating the v-myc avian myelocytomatosis viral (MYC) oncogene. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 8. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND4A	NM_001320835.1	c.1488-890T>C		intron_variant		ENST00000443035.8	NP_001307764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND4A	ENST00000443035.8	c.1488-890T>C		intron_variant		1	NM_001320835.1	ENSP00000391167	A1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122567 AN: 152032 Hom.: 49975 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.802

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122694 AN: 152150 Hom.: 50039 Cov.: 31 AF XY: 0.809 AC XY: 60161 AN XY: 74382

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.805

Alfa AF: 0.755 Hom.: 57306

Bravo AF: 0.816

Asia WGS AF: 0.884 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.36

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: rs934542; hg19: chr15-66016176;