chr1-30935209-T-C

Position:

• chr1-30935209-T-C

Variant summary

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

The NM_001020658.2(PUM1):​c.3435+1434A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,212 control chromosomes in the GnomAD database, including 46,404 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 0.77 (46404 hom., cov: 32)
• Consequence: PUM1 NM_001020658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

Genes affected

PUM1 (HGNC:14957): (pumilio RNA binding family member 1) This gene encodes a member of the PUF family, evolutionarily conserved RNA-binding proteins related to the Pumilio proteins of Drosophila and the fem-3 mRNA binding factor proteins of C. elegans. The encoded protein contains a sequence-specific RNA binding domain comprised of eight repeats and N- and C-terminal flanking regions, and serves as a translational regulator of specific mRNAs by binding to their 3' untranslated regions. The evolutionarily conserved function of the encoded protein in invertebrates and lower vertebrates suggests that the human protein may be involved in translational regulation of embryogenesis, and cell development and differentiation. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PUM1	NM_001020658.2	c.3435+1434A>G		intron_variant		ENST00000426105.7	NP_001018494.1
PUM1	NM_014676.3	c.3429+1434A>G		intron_variant			NP_055491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PUM1	ENST00000426105.7	c.3435+1434A>G		intron_variant		1	NM_001020658.2	ENSP00000391723.2

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117519 AN: 152094 Hom.: 46341 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.773 AC: 117638 AN: 152212 Hom.: 46404 Cov.: 32 AF XY: 0.778 AC XY: 57924 AN XY: 74422

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.715

Alfa AF: 0.700 Hom.: 70458

Bravo AF: 0.763

Asia WGS AF: 0.871 AC: 3029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7514514; hg19: chr1-31408056;