rs1891641

Variant names:

• chr9-123391357-G-A
• rs1891641
• NM_001352964.2:c.1632-3499C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-123391357-G-A
• chr9-123391357-G-C
• chr9-123391357-G-T

Variant summary

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

The NM_001352964.2(DENND1A):​c.1632-3499C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,178 control chromosomes in the GnomAD database, including 2,350 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 0.17 (2350 hom., cov: 33)
• Consequence: DENND1A NM_001352964.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

Genes affected

DENND1A (HGNC:29324): (DENN domain containing 1A) Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND1A	NM_001352964.2	c.1632-3499C>T		intron_variant	Intron 21 of 23	ENST00000394215.7	NP_001339893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND1A	ENST00000394215.7	c.1632-3499C>T		intron_variant	Intron 21 of 23	5	NM_001352964.2	ENSP00000377763.4
DENND1A	ENST00000473039.5	n.1441-3499C>T		intron_variant	Intron 15 of 17	1
DENND1A	ENST00000373624.6	c.1578-7444C>T		intron_variant	Intron 20 of 21	5		ENSP00000362727.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25205 AN: 152060 Hom.: 2339 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.166 AC: 25253 AN: 152178 Hom.: 2350 Cov.: 33 AF XY: 0.168 AC XY: 12518 AN XY: 74402

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.163

Alfa AF: 0.124 Hom.: 1714

Bravo AF: 0.170

Asia WGS AF: 0.0940 AC: 328 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.62

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: rs1891641; hg19: chr9-126153636;