chr9-123398694-A-T

Variant names:

• chr9-123398694-A-T
• rs10818814
• NM_001352964.2:c.1631+4708T>A

Variant summary

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

The ENST00000394215.7(DENND1A):​c.1631+4708T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 149,876 control chromosomes in the GnomAD database, including 13,961 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 0.39 (13961 hom., cov: 31)
• Consequence: DENND1A ENST00000394215.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.943
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394215.7. 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
	DENND1A	NM_001352964.2	MANE Select	c.1631+4708T>A		intron	N/A	NP_001339893.1
	DENND1A	NM_001393654.1		c.1577+4708T>A		intron	N/A	NP_001380583.1
	DENND1A	NM_001352965.2		c.1481+4708T>A		intron	N/A	NP_001339894.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1A	ENST00000394215.7	TSL:5 MANE Select	c.1631+4708T>A		intron	N/A	ENSP00000377763.4
	DENND1A	ENST00000473039.5	TSL:1	n.1440+4708T>A		intron	N/A
	DENND1A	ENST00000373624.6	TSL:5	c.1577+4708T>A		intron	N/A	ENSP00000362727.2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59015 AN: 149762 Hom.: 13969 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.394 AC: 58984 AN: 149876 Hom.: 13961 Cov.: 31 AF XY: 0.391 AC XY: 28645 AN XY: 73170

African (AFR) AF: 0.114 AC: 4592 AN: 40446

American (AMR) AF: 0.402 AC: 6049 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1781 AN: 3462

East Asian (EAS) AF: 0.378 AC: 1870 AN: 4948

South Asian (SAS) AF: 0.367 AC: 1729 AN: 4708

European-Finnish (FIN) AF: 0.490 AC: 5129 AN: 10460

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.538 AC: 36351 AN: 67534

Other (OTH) AF: 0.418 AC: 865 AN: 2070

Alfa AF: 0.455 Hom.: 2238

Bravo AF: 0.365

Asia WGS AF: 0.313 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		0.94
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: rs10818814; hg19: chr9-126160973;