rs10860821

Variant names:

• chr12-101926003-A-G
• rs10860821
• ENST00000549066.1:c.108+11771A>G

Variant summary

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

The ENST00000549066.1(DRAM1):​c.108+11771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,986 control chromosomes in the GnomAD database, including 29,615 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 0.60 (29615 hom., cov: 31)
• Consequence: DRAM1 ENST00000549066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 5 publications found

Genes affected

DRAM1 (HGNC:25645): (DNA damage regulated autophagy modulator 1) This gene is regulated as part of the p53 tumor suppressor pathway. The gene encodes a lysosomal membrane protein that is required for the induction of autophagy by the pathway. Decreased transcriptional expression of this gene is associated with various tumors. This gene has a pseudogene on chromosome 4. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRAM1	ENST00000549066.1	c.108+11771A>G		intron_variant	Intron 2 of 2	3		ENSP00000447906.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91706 AN: 151866 Hom.: 29607 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.604 AC: 91757 AN: 151986 Hom.: 29615 Cov.: 31 AF XY: 0.607 AC XY: 45090 AN XY: 74288

African (AFR) AF: 0.359 AC: 14896 AN: 41448

American (AMR) AF: 0.716 AC: 10925 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2406 AN: 5146

South Asian (SAS) AF: 0.633 AC: 3049 AN: 4818

European-Finnish (FIN) AF: 0.720 AC: 7611 AN: 10572

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48125 AN: 67952

Other (OTH) AF: 0.643 AC: 1360 AN: 2114

Alfa AF: 0.676 Hom.: 150263

Bravo AF: 0.593

Asia WGS AF: 0.542 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.0
DANN	Benign	0.84
PhyloP100		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10860821; hg19: chr12-102319781; COSMIC: COSV51600106;