rs1998598

Positions:

• chr1-197758512-A-G
• chr1-197758512-A-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+14356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,170 control chromosomes in the GnomAD database, including 5,513 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 0.26 (5513 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.82+14356T>C		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+14356T>C		intron_variant		5	NM_001195215.2	ENSP00000479816	P2
	ENST00000440885.1	n.83+1111A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38974 AN: 152052 Hom.: 5505 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.256 AC: 38992 AN: 152170 Hom.: 5513 Cov.: 32 AF XY: 0.250 AC XY: 18582 AN XY: 74412

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.279

Alfa AF: 0.295 Hom.: 8450

Bravo AF: 0.254

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.81

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: rs1998598; hg19: chr1-197727642;