rs4726463

Variant names:

• chr7-141666839-A-G
• rs4726463
• NM_001080392.2:c.682-414T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080392.2(DENND11):​c.682-414T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,154 control chromosomes in the GnomAD database, including 11,235 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 0.36 (11235 hom., cov: 32)
• Consequence: DENND11 NM_001080392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 3 publications found

Genes affected

DENND11 (HGNC:29472): (DENN domain containing 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080392.2. 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
	DENND11	NM_001080392.2	MANE Select	c.682-414T>C		intron	N/A	NP_001073861.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND11	ENST00000536163.6	TSL:1 MANE Select	c.682-414T>C		intron	N/A	ENSP00000445768.1
	DENND11	ENST00000482493.1	TSL:5	c.409-453T>C		intron	N/A	ENSP00000418236.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54234 AN: 152036 Hom.: 11227 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.357 AC: 54254 AN: 152154 Hom.: 11235 Cov.: 32 AF XY: 0.360 AC XY: 26747 AN XY: 74394

African (AFR) AF: 0.135 AC: 5591 AN: 41532

American (AMR) AF: 0.487 AC: 7450 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1378 AN: 3470

East Asian (EAS) AF: 0.560 AC: 2900 AN: 5178

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4820

European-Finnish (FIN) AF: 0.451 AC: 4759 AN: 10556

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29557 AN: 67992

Other (OTH) AF: 0.396 AC: 837 AN: 2112

Alfa AF: 0.407 Hom.: 5908

Bravo AF: 0.356

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.64
PhyloP100		-1.0
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: rs4726463; hg19: chr7-141366639;