chr1-197763925-G-A

Variant names:

• chr1-197763925-G-A
• rs1775456
• NM_001195215.2:c.82+8943C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1B	NM_001195215.2	MANE Select	c.82+8943C>T		intron	N/A	NP_001182144.1	Q6P3S1-1
	DENND1B	NM_144977.5		c.82+8943C>T		intron	N/A	NP_659414.2	Q6P3S1-5
	DENND1B	NM_001300858.2		c.-160+8943C>T		intron	N/A	NP_001287787.1	Q6P3S1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1B	ENST00000620048.6	TSL:5 MANE Select	c.82+8943C>T		intron	N/A	ENSP00000479816.1	Q6P3S1-1
	DENND1B	ENST00000367396.7	TSL:1	c.82+8943C>T		intron	N/A	ENSP00000356366.3	Q6P3S1-5
	DENND1B	ENST00000235453.8	TSL:1	c.-160+8943C>T		intron	N/A	ENSP00000235453.4	Q6P3S1-4

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

African (AFR) AF: 0.955 AC: 39703 AN: 41566

American (AMR) AF: 0.833 AC: 12742 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2709 AN: 3470

East Asian (EAS) AF: 0.888 AC: 4590 AN: 5168

South Asian (SAS) AF: 0.861 AC: 4150 AN: 4820

European-Finnish (FIN) AF: 0.820 AC: 8676 AN: 10586

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54706 AN: 68018

Other (OTH) AF: 0.853 AC: 1806 AN: 2116

Alfa AF: 0.816 Hom.: 25718

Bravo AF: 0.856

Asia WGS AF: 0.888 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.47
PhyloP100		-0.33
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: rs1775456; hg19: chr1-197733055;