chr1-197539771-G-A

Variant names:

• chr1-197539771-G-A
• rs4915551
• NM_001195215.2:c.1515+193C>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.1515+193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,070 control chromosomes in the GnomAD database, including 35,642 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 0.65 (35642 hom., cov: 31)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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.1515+193C>T		intron	N/A	NP_001182144.1
	DENND1B	NR_125340.2		n.1587+193C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND1B	ENST00000620048.6	TSL:5 MANE Select	c.1515+193C>T		intron	N/A	ENSP00000479816.1
	DENND1B	ENST00000887109.1		c.1461+193C>T		intron	N/A	ENSP00000557168.1
	DENND1B	ENST00000887105.1		c.1455+193C>T		intron	N/A	ENSP00000557164.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98375 AN: 151952 Hom.: 35632 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.647 AC: 98407 AN: 152070 Hom.: 35642 Cov.: 31 AF XY: 0.655 AC XY: 48712 AN XY: 74318

African (AFR) AF: 0.290 AC: 12028 AN: 41444

American (AMR) AF: 0.733 AC: 11195 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2559 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4469 AN: 5178

South Asian (SAS) AF: 0.833 AC: 4012 AN: 4816

European-Finnish (FIN) AF: 0.790 AC: 8358 AN: 10582

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.785 AC: 53361 AN: 67986

Other (OTH) AF: 0.698 AC: 1474 AN: 2112

Alfa AF: 0.742 Hom.: 81934

Bravo AF: 0.623

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.39
PhyloP100		-0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4915551; hg19: chr1-197508901;