1-201780563-C-T

Variant names:

• chr1-201780563-C-T
• rs61753857
• NM_001389617.1:c.2226+4C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001389617.1(NAV1):​c.2226+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,614,134 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (24 hom.)
• Consequence: NAV1 NM_001389617.1 splice_region, intron
• Scores: Splicing: ADA: 0.0001371
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06
• Publications: 1 publications found

Genes affected

NAV1 (HGNC:15989): (neuron navigator 1) This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. The exact function of this gene is not known, but it is thought to play a role in in neuronal development and regeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

IPO9-AS1 (HGNC:40892): (IPO9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-201780563-C-T is Benign according to our data. Variant chr1-201780563-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 573 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389617.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	NM_001389617.1	MANE Select	c.2226+4C>T		splice_region intron	N/A	NP_001376546.1	A0A8I5KSE4
	NAV1	NM_001389616.1		c.2226+4C>T		splice_region intron	N/A	NP_001376545.1
	NAV1	NM_001389615.1		c.2226+4C>T		splice_region intron	N/A	NP_001376544.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAV1	ENST00000685211.1	MANE Select	c.2226+4C>T		splice_region intron	N/A	ENSP00000510803.1	A0A8I5KSE4
	NAV1	ENST00000367295.5	TSL:1	c.192+4C>T		splice_region intron	N/A	ENSP00000356264.1	Q8NEY1-5
	NAV1	ENST00000855601.1		c.1434+4C>T		splice_region intron	N/A	ENSP00000525660.1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 572 AN: 152172 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00614

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00376 AC: 946 AN: 251358 AF XY: 0.00393

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00618

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00588 AC: 8602 AN: 1461844 Hom.: 24 Cov.: 33 AF XY: 0.00577 AC XY: 4194 AN XY: 727228

African (AFR) AF: 0.000866 AC: 29 AN: 33480

American (AMR) AF: 0.00154 AC: 69 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0108 AC: 283 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00159 AC: 85 AN: 53414

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00698 AC: 7767 AN: 1111984

Other (OTH) AF: 0.00599 AC: 362 AN: 60396

GnomAD4 genome AF: 0.00376 AC: 573 AN: 152290 Hom.: 4 Cov.: 32 AF XY: 0.00312 AC XY: 232 AN XY: 74474

African (AFR) AF: 0.00118 AC: 49 AN: 41562

American (AMR) AF: 0.00261 AC: 40 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00614 AC: 418 AN: 68024

Other (OTH) AF: 0.00475 AC: 10 AN: 2106

Alfa AF: 0.00579 Hom.: 0

Bravo AF: 0.00408

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00578

EpiControl AF: 0.00593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		-2.1
PromoterAI		-0.0056	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.11		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: rs61753857; hg19: chr1-201749691;