rs11582300

chr1-156669961-G-Achr1-156669961-G-Cchr1-156669961-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006617.2(NES):c.4227C>T(p.Ser1409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,612,362 control chromosomes in the GnomAD database, including 308,953 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 0.57 (25720 hom., cov: 29)
  • Exomes 𝑓: 0.62 (283233 hom.)
• Consequence: NES NM_006617.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

NES (HGNC:7756): (nestin) This gene encodes a member of the intermediate filament protein family and is expressed primarily in nerve cells. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-1.74 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NES	NM_006617.2	c.4227C>T	p.Ser1409=	synonymous_variant	4/4	ENST00000368223.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NES	ENST00000368223.4	c.4227C>T	p.Ser1409=	synonymous_variant	4/4	1	NM_006617.2	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86295 AN: 150830 Hom.: 25705 Cov.: 29

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.612

GnomAD3 exomes AF: 0.630 AC: 156379 AN: 248278 Hom.: 50209 AF XY: 0.626 AC XY: 84448 AN XY: 134822

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.858

Gnomad SAS exome AF: 0.588

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.620 AC: 906039 AN: 1461414 Hom.: 283233 Cov.: 64 AF XY: 0.619 AC XY: 450016 AN XY: 727006

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.804

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.572 AC: 86332 AN: 150948 Hom.: 25720 Cov.: 29 AF XY: 0.577 AC XY: 42522 AN XY: 73716

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.613

Alfa AF: 0.596 Hom.: 19065

Bravo AF: 0.570

Asia WGS AF: 0.722 AC: 2507 AN: 3478

EpiCase AF: 0.618

EpiControl AF: 0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	0.22
Dann	Benign	0.80

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: rs11582300; hg19: chr1-156639753;