chr1-197660212-C-T

Variant names:

• chr1-197660212-C-T
• rs1775453
• NM_001195215.2:c.297-1843G>A

Variant summary

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

The NM_001195215.2(DENND1B):​c.297-1843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,790 control chromosomes in the GnomAD database, including 48,019 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 0.79 (48019 hom., cov: 31)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195215.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1B	NM_001195215.2	MANE Select	c.297-1843G>A		intron	N/A	NP_001182144.1
	DENND1B	NM_144977.5		c.297-1843G>A		intron	N/A	NP_659414.2
	DENND1B	NM_001300858.2		c.267-1843G>A		intron	N/A	NP_001287787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1B	ENST00000620048.6	TSL:5 MANE Select	c.297-1843G>A		intron	N/A	ENSP00000479816.1
	DENND1B	ENST00000367396.7	TSL:1	c.297-1843G>A		intron	N/A	ENSP00000356366.3
	DENND1B	ENST00000235453.8	TSL:1	c.267-1843G>A		intron	N/A	ENSP00000235453.4

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120495 AN: 151672 Hom.: 47969 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.795 AC: 120602 AN: 151790 Hom.: 48019 Cov.: 31 AF XY: 0.798 AC XY: 59157 AN XY: 74174

African (AFR) AF: 0.810 AC: 33554 AN: 41428

American (AMR) AF: 0.785 AC: 11952 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2532 AN: 3468

East Asian (EAS) AF: 0.866 AC: 4477 AN: 5170

South Asian (SAS) AF: 0.855 AC: 4121 AN: 4818

European-Finnish (FIN) AF: 0.802 AC: 8434 AN: 10512

Middle Eastern (MID) AF: 0.825 AC: 241 AN: 292

European-Non Finnish (NFE) AF: 0.781 AC: 53010 AN: 67866

Other (OTH) AF: 0.802 AC: 1693 AN: 2112

Alfa AF: 0.788 Hom.: 7111

Bravo AF: 0.791

Asia WGS AF: 0.871 AC: 3002 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.94
DANN	Benign	0.59
PhyloP100		-0.61
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: rs1775453; hg19: chr1-197629342;