21-41816050-T-G

Position:

• chr21-41816050-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PRDM15	NM_001040424.3	c.2261-214A>C		intron_variant		ENST00000398548.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRDM15	ENST00000398548.6	c.2261-214A>C		intron_variant		1	NM_001040424.3	P2

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

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.860

Alfa AF: 0.875 Hom.: 45805

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6586243; hg19: chr21-43236406;