rs10261374

chr7-141698788-A-T

Variant summary

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

The NM_001080392.2(DENND11):c.268+3098T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,004 control chromosomes in the GnomAD database, including 32,547 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 0.64 (32547 hom., cov: 32)
• Consequence: DENND11 NM_001080392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND11	NM_001080392.2	c.268+3098T>A		intron_variant		ENST00000536163.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND11	ENST00000536163.6	c.268+3098T>A		intron_variant		1	NM_001080392.2	P1
DENND11	ENST00000482493.1	c.-6+2768T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97613 AN: 151886 Hom.: 32522 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.643 AC: 97692 AN: 152004 Hom.: 32547 Cov.: 32 AF XY: 0.643 AC XY: 47739 AN XY: 74266

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.602

Alfa AF: 0.615 Hom.: 3676

Bravo AF: 0.642

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.47
Dann	Benign	0.33

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: rs10261374; hg19: chr7-141398588;