21-41816050-T-G

Variant names:

• chr21-41816050-T-G
• rs6586243
• NM_001040424.3:c.2261-214A>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.2261-214A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,282 control chromosomes in the GnomAD database, including 58,039 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 0.87 (58039 hom., cov: 34)
• Consequence: PRDM15 NM_001040424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 11 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM15	NM_001040424.3	c.2261-214A>C		intron_variant	Intron 18 of 23	ENST00000398548.6	NP_001035514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM15	ENST00000398548.6	c.2261-214A>C		intron_variant	Intron 18 of 23	1	NM_001040424.3	ENSP00000381556.2

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132699 AN: 152164 Hom.: 57984 Cov.: 34

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.872 AC: 132813 AN: 152282 Hom.: 58039 Cov.: 34 AF XY: 0.869 AC XY: 64724 AN XY: 74460

African (AFR) AF: 0.891 AC: 37042 AN: 41554

American (AMR) AF: 0.859 AC: 13141 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2973 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3663 AN: 5170

South Asian (SAS) AF: 0.718 AC: 3463 AN: 4826

European-Finnish (FIN) AF: 0.902 AC: 9577 AN: 10618

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60072 AN: 68016

Other (OTH) AF: 0.860 AC: 1820 AN: 2116

Alfa AF: 0.876 Hom.: 61026

Bravo AF: 0.871

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.44
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6586243; hg19: chr21-43236406;