rs3740094

Positions:

• chr10-44977869-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007021.4(DEPP1):​c.162G>A​(p.Leu54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,611,208 control chromosomes in the GnomAD database, including 21,029 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 0.13 (1556 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19473 hom.)
• Consequence: DEPP1 NM_007021.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

Genes affected

DEPP1 (HGNC:23355): (DEPP autophagy regulator 1) The expression of this gene is induced by fasting as well as by progesterone. The protein encoded by this gene contains a t-synaptosome-associated protein receptor (SNARE) coiled-coil homology domain and a peroxisomal targeting signal. Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. [provided by RefSeq, Jul 2008]

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPP1	NM_007021.4	c.162G>A	p.Leu54=	synonymous_variant	2/2	ENST00000298295.4
RASSF4	NM_032023.4	c.139-4652C>T		intron_variant		ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPP1	ENST00000298295.4	c.162G>A	p.Leu54=	synonymous_variant	2/2	1	NM_007021.4	P1
RASSF4	ENST00000340258.10	c.139-4652C>T		intron_variant		1	NM_032023.4	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19354 AN: 152152 Hom.: 1546 Cov.: 33

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.159 AC: 39538 AN: 248230 Hom.: 3579 AF XY: 0.165 AC XY: 22167 AN XY: 134748

Gnomad AFR exome AF: 0.0320

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.158 AC: 230909 AN: 1458938 Hom.: 19473 Cov.: 33 AF XY: 0.160 AC XY: 116193 AN XY: 725606

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.127 AC: 19373 AN: 152270 Hom.: 1556 Cov.: 33 AF XY: 0.129 AC XY: 9592 AN XY: 74444

Gnomad4 AFR AF: 0.0336

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.161

Alfa AF: 0.154 Hom.: 2552

Bravo AF: 0.121

Asia WGS AF: 0.270 AC: 937 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.70

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: rs3740094; hg19: chr10-45473317; COSMIC: COSV53573583; COSMIC: COSV53573583;