rs4622329

Positions:

• chr12-101928157-G-A
• chr12-101928157-G-C

Variant summary

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

The ENST00000549066.1(DRAM1):​c.109+13925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,908 control chromosomes in the GnomAD database, including 17,229 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 0.46 (17229 hom., cov: 31)
• Consequence: DRAM1 ENST00000549066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRAM1	ENST00000549066.1	c.109+13925G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69187 AN: 151790 Hom.: 17213 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.456 AC: 69251 AN: 151908 Hom.: 17229 Cov.: 31 AF XY: 0.458 AC XY: 33971 AN XY: 74212

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.442

Alfa AF: 0.383 Hom.: 6409

Bravo AF: 0.456

Asia WGS AF: 0.543 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4622329; hg19: chr12-102321935;