rs10507137

chr12-101963532-A-Gchr12-101963532-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549066.1(DRAM1):c.110-48281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,978 control chromosomes in the GnomAD database, including 17,008 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 (17008 hom., cov: 31)
• Consequence: DRAM1 ENST00000549066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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]

LOC107984548 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107984548	XR_001749284.2	n.86+620T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRAM1	ENST00000549066.1	c.110-48281A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70672 AN: 151860 Hom.: 17001 Cov.: 31

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.465 AC: 70705 AN: 151978 Hom.: 17008 Cov.: 31 AF XY: 0.456 AC XY: 33875 AN XY: 74294

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.432

Alfa AF: 0.469 Hom.: 5158

Bravo AF: 0.474

Asia WGS AF: 0.200 AC: 695 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	0.41
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10507137; hg19: chr12-102357310;