chr1-197662011-G-A

Variant names:

• chr1-197662011-G-A
• rs2488389
• NM_001195215.2:c.297-3642C>T

Variant summary

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

The NM_001195215.2(DENND1B):​c.297-3642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,828 control chromosomes in the GnomAD database, including 4,021 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 0.22 (4021 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 49 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.297-3642C>T		intron_variant	Intron 5 of 22	ENST00000620048.6	NP_001182144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6	c.297-3642C>T		intron_variant	Intron 5 of 22	5	NM_001195215.2	ENSP00000479816.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33963 AN: 151710 Hom.: 4011 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.224 AC: 33998 AN: 151828 Hom.: 4021 Cov.: 32 AF XY: 0.220 AC XY: 16332 AN XY: 74226

African (AFR) AF: 0.260 AC: 10770 AN: 41418

American (AMR) AF: 0.202 AC: 3083 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1075 AN: 5174

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1586 AN: 10538

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14928 AN: 67852

Other (OTH) AF: 0.233 AC: 491 AN: 2104

Alfa AF: 0.220 Hom.: 6645

Bravo AF: 0.226

Asia WGS AF: 0.277 AC: 954 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.080
DANN	Benign	0.51
PhyloP100		-2.0
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: rs2488389; hg19: chr1-197631141; COSMIC: COSV52462479; COSMIC: COSV52462479;