chr1-77916353-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144573.4(NEXN):​c.27+220A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 152,232 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 230 hom., cov: 32)

Consequence

NEXN
NM_144573.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.599
Variant links:
Genes affected
NEXN (HGNC:29557): (nexilin F-actin binding protein) This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-77916353-A-C is Benign according to our data. Variant chr1-77916353-A-C is described in ClinVar as [Benign]. Clinvar id is 674339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NEXNNM_144573.4 linkuse as main transcriptc.27+220A>C intron_variant ENST00000334785.12 NP_653174.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.27+220A>C intron_variant 1 NM_144573.4 ENSP00000333938 P3Q0ZGT2-1
NEXNENST00000401035.7 linkuse as main transcriptc.27+220A>C intron_variant 1 ENSP00000383814
NEXNENST00000330010.12 linkuse as main transcriptc.27+220A>C intron_variant 2 ENSP00000327363 A1Q0ZGT2-4
NEXNENST00000440324.5 linkuse as main transcriptc.27+220A>C intron_variant 5 ENSP00000411902

Frequencies

GnomAD3 genomes
AF:
0.0444
AC:
6755
AN:
152114
Hom.:
230
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0891
Gnomad AMI
AF:
0.00659
Gnomad AMR
AF:
0.0366
Gnomad ASJ
AF:
0.0518
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0129
Gnomad FIN
AF:
0.0123
Gnomad MID
AF:
0.0759
Gnomad NFE
AF:
0.0294
Gnomad OTH
AF:
0.0511
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0443
AC:
6749
AN:
152232
Hom.:
230
Cov.:
32
AF XY:
0.0419
AC XY:
3119
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.0888
Gnomad4 AMR
AF:
0.0364
Gnomad4 ASJ
AF:
0.0518
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0125
Gnomad4 FIN
AF:
0.0123
Gnomad4 NFE
AF:
0.0294
Gnomad4 OTH
AF:
0.0511
Alfa
AF:
0.0387
Hom.:
20
Bravo
AF:
0.0486
Asia WGS
AF:
0.0130
AC:
44
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
5.1
DANN
Benign
0.67

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs74092331; hg19: chr1-78382038; API