chr1-77888900-G-T

Variant summary

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

The NM_144573.4(NEXN):​c.-53+141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,428 control chromosomes in the GnomAD database, including 6,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6195 hom., cov: 32)
Exomes 𝑓: 0.20 ( 9 hom. )

Consequence

NEXN
NM_144573.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.467
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]
NEXN-AS1 (HGNC:31983): (NEXN antisense RNA 1)

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=-0.8).
BP6
Variant 1-77888900-G-T is Benign according to our data. Variant chr1-77888900-G-T is described in ClinVar as [Benign]. Clinvar id is 1233836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEXNNM_144573.4 linkuse as main transcriptc.-53+141G>T intron_variant ENST00000334785.12
NEXN-AS1NR_103535.1 linkuse as main transcriptn.441C>A non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEXNENST00000334785.12 linkuse as main transcriptc.-53+141G>T intron_variant 1 NM_144573.4 P3Q0ZGT2-1
NEXN-AS1ENST00000421331.1 linkuse as main transcriptn.441C>A non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
AF:
0.277
AC:
42167
AN:
151978
Hom.:
6192
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.364
Gnomad AMI
AF:
0.260
Gnomad AMR
AF:
0.200
Gnomad ASJ
AF:
0.271
Gnomad EAS
AF:
0.395
Gnomad SAS
AF:
0.187
Gnomad FIN
AF:
0.201
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.253
Gnomad OTH
AF:
0.255
GnomAD4 exome
AF:
0.200
AC:
66
AN:
330
Hom.:
9
Cov.:
0
AF XY:
0.198
AC XY:
51
AN XY:
258
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.500
Gnomad4 EAS exome
AF:
0.375
Gnomad4 SAS exome
AF:
0.214
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.199
Gnomad4 OTH exome
AF:
0.167
GnomAD4 genome
AF:
0.277
AC:
42184
AN:
152098
Hom.:
6195
Cov.:
32
AF XY:
0.271
AC XY:
20166
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.364
Gnomad4 AMR
AF:
0.200
Gnomad4 ASJ
AF:
0.271
Gnomad4 EAS
AF:
0.395
Gnomad4 SAS
AF:
0.188
Gnomad4 FIN
AF:
0.201
Gnomad4 NFE
AF:
0.253
Gnomad4 OTH
AF:
0.252
Alfa
AF:
0.283
Hom.:
912
Bravo
AF:
0.285
Asia WGS
AF:
0.262
AC:
907
AN:
3474

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 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.98
DANN
Benign
0.52

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: rs9726525; hg19: chr1-78354585; API