rs1775456

Positions:

• chr1-197763925-G-A

Variant summary

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

The NM_001195215.2(DENND1B):​c.82+8943C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,248 control chromosomes in the GnomAD database, including 55,859 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 0.85 (55859 hom., cov: 33)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND1B	NM_001195215.2	c.82+8943C>T		intron_variant		ENST00000620048.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND1B	ENST00000620048.6	c.82+8943C>T		intron_variant		5	NM_001195215.2	P2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129831 AN: 152130 Hom.: 55801 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.854 AC: 129947 AN: 152248 Hom.: 55859 Cov.: 33 AF XY: 0.856 AC XY: 63696 AN XY: 74418

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.853

Alfa AF: 0.819 Hom.: 23267

Bravo AF: 0.856

Asia WGS AF: 0.888 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.47

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: rs1775456; hg19: chr1-197733055;