rs4622329

Variant names:

• chr12-101928157-G-A
• rs4622329
• ENST00000549066.1:c.108+13925G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000549066.1(DRAM1):​c.108+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
• Publications: 26 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=-0.73).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRAM1	ENST00000549066.1	c.108+13925G>A		intron_variant	Intron 2 of 2	3		ENSP00000447906.1

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

African (AFR) AF: 0.651 AC: 26932 AN: 41400

American (AMR) AF: 0.336 AC: 5130 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3011 AN: 5164

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4812

European-Finnish (FIN) AF: 0.448 AC: 4725 AN: 10542

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24376 AN: 67924

Other (OTH) AF: 0.442 AC: 936 AN: 2116

Alfa AF: 0.397 Hom.: 24581

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
PhyloP100		0.073

Splicing

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

Other links and lift over

dbSNP: rs4622329; hg19: chr12-102321935;