chr21-41855386-A-G

Variant names:

• chr21-41855386-A-G
• rs915832
• NM_001040424.3:c.286-568T>C

Variant summary

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

The NM_001040424.3(PRDM15):​c.286-568T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,098 control chromosomes in the GnomAD database, including 40,237 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 0.72 (40237 hom., cov: 32)
• Consequence: PRDM15 NM_001040424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 9 publications found

Genes affected

PRDM15 (HGNC:13999): (PR/SET domain 15) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and promoter-specific chromatin binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II; regulation of signal transduction; and regulation of stem cell division. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	NM_001040424.3	MANE Select	c.286-568T>C		intron	N/A	NP_001035514.2
	PRDM15	NM_022115.7		c.484-568T>C		intron	N/A	NP_071398.5
	PRDM15	NM_001282934.2		c.286-568T>C		intron	N/A	NP_001269863.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDM15	ENST00000398548.6	TSL:1 MANE Select	c.286-568T>C		intron	N/A	ENSP00000381556.2
	PRDM15	ENST00000269844.5	TSL:1	c.484-568T>C		intron	N/A	ENSP00000269844.4
	PRDM15	ENST00000422911.6	TSL:1	c.286-568T>C		intron	N/A	ENSP00000408592.2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110099 AN: 151980 Hom.: 40210 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.724 AC: 110180 AN: 152098 Hom.: 40237 Cov.: 32 AF XY: 0.724 AC XY: 53875 AN XY: 74366

African (AFR) AF: 0.653 AC: 27078 AN: 41472

American (AMR) AF: 0.803 AC: 12280 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2650 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2778 AN: 5154

South Asian (SAS) AF: 0.629 AC: 3036 AN: 4824

European-Finnish (FIN) AF: 0.763 AC: 8076 AN: 10590

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51864 AN: 67968

Other (OTH) AF: 0.741 AC: 1567 AN: 2114

Alfa AF: 0.748 Hom.: 109531

Bravo AF: 0.728

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.71
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs915832; hg19: chr21-43275495;