rs2488393

Positions:

• chr1-197753110-C-T

Variant summary

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

The NM_001195215.2(DENND1B):​c.82+19758G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,720 control chromosomes in the GnomAD database, including 4,242 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 0.23 (4242 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.34

Genes affected

DENND1B (HGNC:28404): (DENN domain containing 1B) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.82+19758G>A		intron_variant		ENST00000620048.6	NP_001182144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6	c.82+19758G>A		intron_variant		5	NM_001195215.2	ENSP00000479816	P2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34242 AN: 151602 Hom.: 4238 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.226 AC: 34262 AN: 151720 Hom.: 4242 Cov.: 32 AF XY: 0.221 AC XY: 16368 AN XY: 74174

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.235

Alfa AF: 0.223 Hom.: 452

Bravo AF: 0.230

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.63

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: rs2488393; hg19: chr1-197722240; COSMIC: COSV52462526; COSMIC: COSV52462526;