1-25905865-C-A

Position:

• chr1-25905865-C-A

Variant summary

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

The NM_203401.2(STMN1):​c.-76G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,194 control chromosomes in the GnomAD database, including 32,773 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 0.65 (32745 hom., cov: 34)
  • Exomes 𝑓: 0.69 (28 hom.)
• Consequence: STMN1 NM_203401.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

Genes affected

STMN1 (HGNC:6510): (stathmin 1) This gene belongs to the stathmin family of genes. It encodes a ubiquitous cytosolic phosphoprotein proposed to function as an intracellular relay integrating regulatory signals of the cellular environment. The encoded protein is involved in the regulation of the microtubule filament system by destabilizing microtubules. It prevents assembly and promotes disassembly of microtubules. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

STMN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STMN1	NM_005563.4	c.-63+524G>T		intron_variant		ENST00000455785.7	NP_005554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STMN1	ENST00000455785.7	c.-63+524G>T		intron_variant		1	NM_005563.4	ENSP00000387858.2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98488 AN: 151952 Hom.: 32683 Cov.: 34

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.618

GnomAD4 exome AF: 0.694 AC: 86 AN: 124 Hom.: 28 Cov.: 0 AF XY: 0.708 AC XY: 68 AN XY: 96

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.649

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.648 AC: 98614 AN: 152070 Hom.: 32745 Cov.: 34 AF XY: 0.648 AC XY: 48173 AN XY: 74358

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.618

Alfa AF: 0.637 Hom.: 7664

Bravo AF: 0.660

Asia WGS AF: 0.758 AC: 2637 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.3
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs213641; hg19: chr1-26232356;