NM_001393612.1:c.-1210-9151A>G

Variant names:

• chr22-29397652-A-G
• rs2267138
• NM_001393612.1:c.-1210-9151A>G

Variant summary

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

The NM_001393612.1(RFPL1):​c.-1210-9151A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,178 control chromosomes in the GnomAD database, including 1,355 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 0.12 (1355 hom., cov: 32)
• Consequence: RFPL1 NM_001393612.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 8 publications found

Genes affected

RFPL1 (HGNC:9977): (ret finger protein like 1) Predicted to enable ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of G2/M transition of mitotic cell cycle; negative regulation of cell division; and positive regulation of proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290778 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFPL1	NM_001393612.1	c.-1210-9151A>G		intron_variant	Intron 1 of 9		NP_001380541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290778	ENST00000650462.1	n.189-9151A>G		intron_variant	Intron 1 of 6
ENSG00000290778	ENST00000752284.1	n.130+36455A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18914 AN: 152060 Hom.: 1353 Cov.: 32

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.124 AC: 18928 AN: 152178 Hom.: 1355 Cov.: 32 AF XY: 0.125 AC XY: 9308 AN XY: 74418

African (AFR) AF: 0.0973 AC: 4039 AN: 41510

American (AMR) AF: 0.103 AC: 1574 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1624 AN: 5154

South Asian (SAS) AF: 0.100 AC: 484 AN: 4826

European-Finnish (FIN) AF: 0.145 AC: 1542 AN: 10612

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8670 AN: 67994

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.127 Hom.: 2829

Bravo AF: 0.122

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2267138; hg19: chr22-29793641;