rs1446453046

Variant names:

• chr20-38057588-G-A
• rs1446453046
• NM_021215.4:c.472G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-38057588-G-A
• chr20-38057588-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021215.4(RPRD1B):​c.472G>A​(p.Asp158Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D158H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RPRD1B NM_021215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29

Genes affected

RPRD1B (HGNC:16209): (regulation of nuclear pre-mRNA domain containing 1B) Enables RNA polymerase II complex binding activity and identical protein binding activity. Involved in positive regulation of cell population proliferation; regulation of cell cycle process; and regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of RNA polymerase II, holoenzyme. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18687665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPRD1B	NM_021215.4	c.472G>A	p.Asp158Asn	missense_variant	Exon 4 of 7	ENST00000373433.9	NP_067038.1
RPRD1B	XM_047440346.1	c.148G>A	p.Asp50Asn	missense_variant	Exon 2 of 5		XP_047296302.1
RPRD1B	XM_047440347.1	c.73G>A	p.Asp25Asn	missense_variant	Exon 2 of 5		XP_047296303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPRD1B	ENST00000373433.9	c.472G>A	p.Asp158Asn	missense_variant	Exon 4 of 7	1	NM_021215.4	ENSP00000362532.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461856 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	0.012
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.98	L;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.075
Sift	Benign	0.61	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0090	B;.
Vest4		0.19
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0275);.;
MVP		0.16
MPC		0.89
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.42

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: rs1446453046; hg19: chr20-36685990; COSMIC: COSV65032352;