10-44977869-C-T

Variant names:

• chr10-44977869-C-T
• rs3740094
• NM_007021.4:c.162G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007021.4(DEPP1):​c.162G>A​(p.Leu54Leu) 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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DEPP1	NM_007021.4	c.162G>A	p.Leu54Leu	synonymous_variant	Exon 2 of 2	ENST00000298295.4	NP_008952.1
RASSF4	NM_032023.4	c.139-4652C>T		intron_variant	Intron 3 of 10	ENST00000340258.10	NP_114412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPP1	ENST00000298295.4	c.162G>A	p.Leu54Leu	synonymous_variant	Exon 2 of 2	1	NM_007021.4	ENSP00000298295.3
RASSF4	ENST00000340258.10	c.139-4652C>T		intron_variant	Intron 3 of 10	1	NM_032023.4	ENSP00000339692.4

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

GnomAD2 exomes AF: 0.159 AC: 39538 AN: 248230 AF XY: 0.165

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 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

African (AFR) AF: 0.0278 AC: 928 AN: 33402

American (AMR) AF: 0.106 AC: 4707 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4357 AN: 26044

East Asian (EAS) AF: 0.319 AC: 12668 AN: 39672

South Asian (SAS) AF: 0.191 AC: 16426 AN: 86136

European-Finnish (FIN) AF: 0.160 AC: 8356 AN: 52326

Middle Eastern (MID) AF: 0.162 AC: 935 AN: 5754

European-Non Finnish (NFE) AF: 0.156 AC: 172840 AN: 1111052

Other (OTH) AF: 0.161 AC: 9692 AN: 60238

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

African (AFR) AF: 0.0336 AC: 1399 AN: 41590

American (AMR) AF: 0.113 AC: 1732 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5166

South Asian (SAS) AF: 0.203 AC: 978 AN: 4826

European-Finnish (FIN) AF: 0.158 AC: 1677 AN: 10604

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10978 AN: 67982

Other (OTH) AF: 0.161 AC: 341 AN: 2116

Alfa AF: 0.151 Hom.: 3410

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
PhyloP100		-0.25
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: rs3740094; hg19: chr10-45473317; COSMIC: COSV53573583; COSMIC: COSV53573583;