15-65723838-A-G

Variant names:

• chr15-65723838-A-G
• rs934542
• NM_001320835.1:c.1488-890T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320835.1. 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
	DENND4A	NM_001320835.1	MANE Select	c.1488-890T>C		intron	N/A	NP_001307764.1
	DENND4A	NM_001144823.2		c.1488-890T>C		intron	N/A	NP_001138295.1
	DENND4A	NM_001376919.1		c.1488-890T>C		intron	N/A	NP_001363848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND4A	ENST00000443035.8	TSL:1 MANE Select	c.1488-890T>C		intron	N/A	ENSP00000391167.4
	DENND4A	ENST00000431932.6	TSL:1	c.1488-890T>C		intron	N/A	ENSP00000396830.2
	DENND4A	ENST00000564674.5	TSL:1	c.1488-890T>C		intron	N/A	ENSP00000457358.1

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

African (AFR) AF: 0.926 AC: 38440 AN: 41534

American (AMR) AF: 0.802 AC: 12254 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4849 AN: 5182

South Asian (SAS) AF: 0.827 AC: 3984 AN: 4816

European-Finnish (FIN) AF: 0.757 AC: 8002 AN: 10564

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50016 AN: 67984

Other (OTH) AF: 0.805 AC: 1699 AN: 2110

Alfa AF: 0.764 Hom.: 81997

Bravo AF: 0.816

Asia WGS AF: 0.884 AC: 3076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-1.5
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: rs934542; hg19: chr15-66016176;