1-197756243-C-T

Position:

• chr1-197756243-C-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+16625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,112 control chromosomes in the GnomAD database, including 1,734 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 0.11 (1734 hom., cov: 31)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND1B	NM_001195215.2	c.82+16625G>A		intron_variant		ENST00000620048.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND1B	ENST00000620048.6	c.82+16625G>A		intron_variant		5	NM_001195215.2	P2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17403 AN: 151994 Hom.: 1726 Cov.: 31

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.114 AC: 17411 AN: 152112 Hom.: 1734 Cov.: 31 AF XY: 0.124 AC XY: 9245 AN XY: 74356

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.0868

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.115

Alfa AF: 0.109 Hom.: 841

Bravo AF: 0.109

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.43

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: rs10922273; hg19: chr1-197725373;