1-197642552-C-A

Position:

• chr1-197642552-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001195215.2(DENND1B):​c.672+159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,116 control chromosomes in the GnomAD database, including 2,599 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 0.17 (2599 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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]

DENND1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.672+159G>T		intron_variant		ENST00000620048.6	NP_001182144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6	c.672+159G>T		intron_variant		5	NM_001195215.2	ENSP00000479816.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25306 AN: 151998 Hom.: 2593 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.166 AC: 25313 AN: 152116 Hom.: 2599 Cov.: 32 AF XY: 0.165 AC XY: 12241 AN XY: 74350

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.197

Alfa AF: 0.186 Hom.: 1344

Bravo AF: 0.161

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.76

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: rs16841842; hg19: chr1-197611682;