Genetic Variant ENST00000614670.1:c.175-17577G>T (chr20-38048679-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021215.4(RPRD1B):c.415+198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,140 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.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Consequence

RPRD1B
NM_021215.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.314

Variant links:

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]

RPRD1B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RPRD1B	NM_021215.4 link	c.415+198C>T	intron_variant	Intron 3 of 6	ENST00000373433.9	NP_067038.1	Q9NQG5
RPRD1B	XM_047440346.1 link	c.91+8115C>T	intron_variant	Intron 1 of 4		XP_047296302.1
RPRD1B	XM_047440347.1 link	c.16+61C>T	intron_variant	Intron 1 of 4		XP_047296303.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RPRD1B	ENST00000373433.9 link	c.415+198C>T	intron_variant	Intron 3 of 6	1	NM_021215.4	ENSP00000362532.4	Q9NQG5
RPRD1B	ENST00000462548.6 link	n.*102+198C>T	intron_variant	Intron 2 of 5	5		ENSP00000436816.1	E9PQF3
RPRD1B	ENST00000495457.1 link	n.281+8115C>T	intron_variant	Intron 2 of 3	4		ENSP00000433947.1	E9PIQ9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over