9-19279855-A-T

Variant names:

• chr9-19279855-A-T
• rs10811161
• NM_001330640.2:c.305+3376A>T

Variant summary

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

The NM_001330640.2(DENND4C):​c.305+3376A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,524 control chromosomes in the GnomAD database, including 18,806 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 0.49 (18806 hom., cov: 29)
• Consequence: DENND4C NM_001330640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 publications found

Genes affected

DENND4C (HGNC:26079): (DENN domain containing 4C) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in cellular response to insulin stimulus; protein localization to plasma membrane; and regulation of Rab protein signal transduction. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND4C	NM_001330640.2	c.305+3376A>T		intron_variant	Intron 2 of 32	ENST00000434457.7	NP_001317569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND4C	ENST00000434457.7	c.305+3376A>T		intron_variant	Intron 2 of 32	5	NM_001330640.2	ENSP00000473469.1
DENND4C	ENST00000602925.5	c.305+3376A>T		intron_variant	Intron 2 of 31	5		ENSP00000473565.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 73958 AN: 151406 Hom.: 18806 Cov.: 29

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.488 AC: 73965 AN: 151524 Hom.: 18806 Cov.: 29 AF XY: 0.490 AC XY: 36254 AN XY: 73972

African (AFR) AF: 0.327 AC: 13483 AN: 41262

American (AMR) AF: 0.538 AC: 8185 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.546 AC: 2799 AN: 5128

South Asian (SAS) AF: 0.646 AC: 3105 AN: 4804

European-Finnish (FIN) AF: 0.511 AC: 5338 AN: 10450

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37242 AN: 67900

Other (OTH) AF: 0.487 AC: 1024 AN: 2102

Alfa AF: 0.361 Hom.: 924

Bravo AF: 0.481

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.66
PhyloP100		-1.1
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: rs10811161; hg19: chr9-19279853;