chr1-197588143-C-G

Variant names:

• chr1-197588143-C-G
• rs12094462
• NM_001195215.2:c.1048-4890G>C

Variant summary

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

The NM_001195215.2(DENND1B):​c.1048-4890G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,204 control chromosomes in the GnomAD database, including 542 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 0.077 (542 hom., cov: 32)
• Consequence: DENND1B NM_001195215.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1B	NM_001195215.2	c.1048-4890G>C		intron_variant	Intron 14 of 22	ENST00000620048.6	NP_001182144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1B	ENST00000620048.6	c.1048-4890G>C		intron_variant	Intron 14 of 22	5	NM_001195215.2	ENSP00000479816.1
DENND1B	ENST00000367396.7	c.1048-4890G>C		intron_variant	Intron 14 of 15	1		ENSP00000356366.3
DENND1B	ENST00000235453.8	c.958-4890G>C		intron_variant	Intron 14 of 15	1		ENSP00000235453.4
DENND1B	ENST00000294737.11	n.987+7065G>C		intron_variant	Intron 13 of 19	2		ENSP00000294737.7

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11666 AN: 152086 Hom.: 542 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0767 AC: 11674 AN: 152204 Hom.: 542 Cov.: 32 AF XY: 0.0740 AC XY: 5505 AN XY: 74414

African (AFR) AF: 0.0621 AC: 2579 AN: 41524

American (AMR) AF: 0.0699 AC: 1068 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4822

European-Finnish (FIN) AF: 0.0648 AC: 686 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0981 AC: 6675 AN: 68016

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0823 Hom.: 58

Bravo AF: 0.0781

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.18
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: rs12094462; hg19: chr1-197557273;