rs7971536

Variant names:

• chr12-101980010-T-A
• rs7971536
• ENST00000549066.1:c.109-31803T>A

Variant summary

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

The ENST00000549066.1(DRAM1):​c.109-31803T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,052 control chromosomes in the GnomAD database, including 16,825 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 (16825 hom., cov: 32)
• Consequence: DRAM1 ENST00000549066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 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.109-31803T>A		intron_variant	Intron 2 of 2	3		ENSP00000447906.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70395 AN: 151936 Hom.: 16819 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.463 AC: 70433 AN: 152052 Hom.: 16825 Cov.: 32 AF XY: 0.453 AC XY: 33640 AN XY: 74336

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.439

Alfa AF: 0.476 Hom.: 2125

Bravo AF: 0.471

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7971536; hg19: chr12-102373788;