rs1928482

Variant names:

• chr9-123670169-T-C
• rs1928482
• NM_001352964.2:c.453+1122A>G

Variant summary

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

The NM_001352964.2(DENND1A):​c.453+1122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,070 control chromosomes in the GnomAD database, including 20,798 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 0.49 (20798 hom., cov: 32)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742
• Publications: 6 publications found

Genes affected

DENND1A (HGNC:29324): (DENN domain containing 1A) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.453+1122A>G		intron_variant	Intron 7 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.453+1122A>G		intron_variant	Intron 7 of 23	5	NM_001352964.2	ENSP00000377763.4

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74546 AN: 151952 Hom.: 20735 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.491 AC: 74678 AN: 152070 Hom.: 20798 Cov.: 32 AF XY: 0.492 AC XY: 36562 AN XY: 74316

African (AFR) AF: 0.767 AC: 31814 AN: 41486

American (AMR) AF: 0.421 AC: 6436 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1105 AN: 5174

South Asian (SAS) AF: 0.356 AC: 1719 AN: 4822

European-Finnish (FIN) AF: 0.462 AC: 4878 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26036 AN: 67972

Other (OTH) AF: 0.447 AC: 943 AN: 2110

Alfa AF: 0.505 Hom.: 3242

Bravo AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.87
PhyloP100		-0.74
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: rs1928482; hg19: chr9-126432448;