1-31066204-A-G

Variant names:

• chr1-31066204-A-G
• rs7526662
• ENST00000373741.8:c.-419T>C

Variant summary

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

The ENST00000373741.8(PUM1):​c.-419T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,156 control chromosomes in the GnomAD database, including 9,425 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 0.31 (9425 hom., cov: 32)
• Consequence: PUM1 ENST00000373741.8 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 1 publications found

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]

PUM1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• spinocerebellar ataxia 47

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373741.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUM1	ENST00000373741.8	TSL:1	c.-419T>C		upstream_gene	N/A	ENSP00000362846.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46371 AN: 152038 Hom.: 9404 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.305 AC: 46436 AN: 152156 Hom.: 9425 Cov.: 32 AF XY: 0.306 AC XY: 22760 AN XY: 74416

African (AFR) AF: 0.559 AC: 23179 AN: 41482

American (AMR) AF: 0.175 AC: 2671 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2823 AN: 5162

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4828

European-Finnish (FIN) AF: 0.218 AC: 2315 AN: 10596

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12433 AN: 68000

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.214 Hom.: 2603

Bravo AF: 0.312

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.64
PhyloP100		0.053
PromoterAI		0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7526662; hg19: chr1-31539051;