rs13231650

Positions:

• chr7-141699142-T-C

Variant summary

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

The NM_001080392.2(DENND11):​c.268+2744A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,910 control chromosomes in the GnomAD database, including 30,907 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 0.63 (30907 hom., cov: 30)
• Consequence: DENND11 NM_001080392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND11	NM_001080392.2	c.268+2744A>G		intron_variant		ENST00000536163.6	NP_001073861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND11	ENST00000536163.6	c.268+2744A>G		intron_variant		1	NM_001080392.2	ENSP00000445768.1
DENND11	ENST00000482493.1	c.-6+2414A>G		intron_variant		5		ENSP00000418236.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95447 AN: 151792 Hom.: 30887 Cov.: 30

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.629 AC: 95519 AN: 151910 Hom.: 30907 Cov.: 30 AF XY: 0.629 AC XY: 46712 AN XY: 74254

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.590

Alfa AF: 0.570 Hom.: 41653

Bravo AF: 0.625

Asia WGS AF: 0.605 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.57

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: rs13231650; hg19: chr7-141398942;