rs4915551

Positions:

• chr1-197539771-G-A
• chr1-197539771-G-C
• chr1-197539771-G-T

Variant summary

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

The NM_001195215.2(DENND1B):​c.1515+193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,070 control chromosomes in the GnomAD database, including 35,642 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 0.65 (35642 hom., cov: 31)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.1515+193C>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.1515+193C>T		intron_variant		5	NM_001195215.2	ENSP00000479816	P2
DENND1B	ENST00000294737.11	c.*203+193C>T		intron_variant, NMD_transcript_variant		2		ENSP00000294737

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98375 AN: 151952 Hom.: 35632 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.647 AC: 98407 AN: 152070 Hom.: 35642 Cov.: 31 AF XY: 0.655 AC XY: 48712 AN XY: 74318

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.698

Alfa AF: 0.758 Hom.: 61251

Bravo AF: 0.623

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4915551; hg19: chr1-197508901;