rs10494757

Variant names:

• chr1-197538281-C-T
• rs10494757
• NM_001195215.2:c.1515+1683G>A

Variant summary

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

The NM_001195215.2(DENND1B):​c.1515+1683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 151,900 control chromosomes in the GnomAD database, including 240 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 0.046 (240 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.1515+1683G>A		intron_variant	Intron 20 of 22	ENST00000620048.6	NP_001182144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6	c.1515+1683G>A		intron_variant	Intron 20 of 22	5	NM_001195215.2	ENSP00000479816.1
DENND1B	ENST00000294737.11	n.*203+1683G>A		intron_variant	Intron 17 of 19	2		ENSP00000294737.7

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7050 AN: 151782 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0175

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0464 AC: 7052 AN: 151900 Hom.: 240 Cov.: 32 AF XY: 0.0454 AC XY: 3370 AN XY: 74222

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0177

Gnomad4 FIN AF: 0.0628

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0650 Hom.: 250

Bravo AF: 0.0431

Asia WGS AF: 0.0120 AC: 40 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10494757; hg19: chr1-197507411;