rs1163087

Positions:

• chr10-103283532-G-A

Variant summary

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

The NM_032727.4(INA):​c.1066-3503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,876 control chromosomes in the GnomAD database, including 11,434 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 0.37 (11434 hom., cov: 32)
• Consequence: INA NM_032727.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

Genes affected

INA (HGNC:6057): (internexin neuronal intermediate filament protein alpha) Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene is a member of the intermediate filament family and is involved in the morphogenesis of neurons. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INA	NM_032727.4	c.1066-3503G>A		intron_variant		ENST00000369849.9	NP_116116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INA	ENST00000369849.9	c.1066-3503G>A		intron_variant		1	NM_032727.4	ENSP00000358865.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55984 AN: 151760 Hom.: 11432 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.369 AC: 56002 AN: 151876 Hom.: 11434 Cov.: 32 AF XY: 0.374 AC XY: 27788 AN XY: 74218

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.385

Alfa AF: 0.424 Hom.: 13798

Bravo AF: 0.352

Asia WGS AF: 0.483 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.84

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: rs1163087; hg19: chr10-105043289;