chr1-68480347-A-C

Variant names:

• chr1-68480347-A-C
• rs10493446
• NM_001114120.3:c.1936-1027T>G

Variant summary

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

The NM_001114120.3(DEPDC1):​c.1936-1027T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,682 control chromosomes in the GnomAD database, including 18,156 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 0.47 (18156 hom., cov: 31)
• Consequence: DEPDC1 NM_001114120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 2 publications found

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233589 (HGNC:58135):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1	NM_001114120.3	c.1936-1027T>G		intron_variant	Intron 9 of 11	ENST00000456315.7	NP_001107592.1
DEPDC1	NM_017779.6	c.1084-1027T>G		intron_variant	Intron 8 of 10		NP_060249.2
DEPDC1-AS2	NR_198991.1	n.181+1038A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC1	ENST00000456315.7	c.1936-1027T>G		intron_variant	Intron 9 of 11	1	NM_001114120.3	ENSP00000412292.2

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71685 AN: 151562 Hom.: 18163 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.473 AC: 71678 AN: 151682 Hom.: 18156 Cov.: 31 AF XY: 0.461 AC XY: 34137 AN XY: 74098

African (AFR) AF: 0.388 AC: 16047 AN: 41350

American (AMR) AF: 0.434 AC: 6599 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2455 AN: 3460

East Asian (EAS) AF: 0.114 AC: 589 AN: 5148

South Asian (SAS) AF: 0.356 AC: 1708 AN: 4804

European-Finnish (FIN) AF: 0.399 AC: 4202 AN: 10520

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38268 AN: 67878

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.546 Hom.: 25656

Bravo AF: 0.471

Asia WGS AF: 0.263 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.37
PhyloP100		3.1
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: rs10493446; hg19: chr1-68946030;