chr1-30998855-A-C

Variant names:

• chr1-30998855-A-C
• rs7536851
• NM_001020658.2:c.721-3635T>G

Variant summary

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

The NM_001020658.2(PUM1):​c.721-3635T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,030 control chromosomes in the GnomAD database, including 7,998 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 0.28 (7998 hom., cov: 31)
• Consequence: PUM1 NM_001020658.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PUM1	NM_001020658.2	c.721-3635T>G		intron_variant	Intron 5 of 21	ENST00000426105.7	NP_001018494.1
PUM1	NM_014676.3	c.721-3635T>G		intron_variant	Intron 5 of 21		NP_055491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUM1	ENST00000426105.7	c.721-3635T>G		intron_variant	Intron 5 of 21	1	NM_001020658.2	ENSP00000391723.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43230 AN: 151912 Hom.: 7982 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.285 AC: 43271 AN: 152030 Hom.: 7998 Cov.: 31 AF XY: 0.285 AC XY: 21216 AN XY: 74348

African (AFR) AF: 0.504 AC: 20846 AN: 41398

American (AMR) AF: 0.163 AC: 2489 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2714 AN: 5150

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4814

European-Finnish (FIN) AF: 0.215 AC: 2271 AN: 10582

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12052 AN: 68002

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.198 Hom.: 6102

Bravo AF: 0.290

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.8
DANN	Benign	0.61
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7536851; hg19: chr1-31471702;