22-29442214-A-T

Position:

• chr22-29442214-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021026.2(RFPL1):​c.*92A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 892,150 control chromosomes in the GnomAD database, including 13,485 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 0.17 (2237 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11248 hom.)
• Consequence: RFPL1 NM_021026.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733

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]

RFPL1S (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL1	NM_021026.2	c.*92A>T		3_prime_UTR_variant	2/2		NP_066306.2
RFPL1	NM_001393612.1	c.*92A>T		3_prime_UTR_variant	10/10		NP_001380541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL1	ENST00000354373.2	c.*92A>T		3_prime_UTR_variant	2/2	1		ENSP00000346342.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25232 AN: 152020 Hom.: 2231 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.168 AC: 124621 AN: 740012 Hom.: 11248 Cov.: 10 AF XY: 0.166 AC XY: 61542 AN XY: 371052

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.0897

Gnomad4 ASJ exome AF: 0.0859

Gnomad4 EAS exome AF: 0.0218

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.166 AC: 25273 AN: 152138 Hom.: 2237 Cov.: 32 AF XY: 0.160 AC XY: 11927 AN XY: 74370

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.158

Alfa AF: 0.183 Hom.: 300

Bravo AF: 0.164

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.31

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: rs13053624; hg19: chr22-29838203;