rs3767028

chr1-77942851-C-Gchr1-77942851-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144573.4(NEXN):c.*22C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,578,918 control chromosomes in the GnomAD database, including 7,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (981 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6395 hom.)
• Consequence: NEXN NM_144573.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-77942851-C-G is Benign according to our data. Variant chr1-77942851-C-G is described in ClinVar as [Benign]. Clinvar id is 1239494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEXN	NM_144573.4	c.*22C>G		3_prime_UTR_variant	13/13	ENST00000334785.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXN	ENST00000334785.12	c.*22C>G		3_prime_UTR_variant	13/13	1	NM_144573.4	P3
NEXN	ENST00000342754.5	c.1716+33C>G		intron_variant		1
NEXN	ENST00000330010.12	c.*22C>G		3_prime_UTR_variant	12/12	2		A1
NEXN	ENST00000480732.2	n.1624C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16035 AN: 151802 Hom.: 974 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.122 AC: 26418 AN: 215808 Hom.: 1971 AF XY: 0.118 AC XY: 13824 AN XY: 117360

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.0868

Gnomad EAS exome AF: 0.0938

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.0850

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0876 AC: 125063 AN: 1426998 Hom.: 6395 Cov.: 28 AF XY: 0.0880 AC XY: 62434 AN XY: 709358

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.0891

Gnomad4 EAS exome AF: 0.0821

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0764

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.106 AC: 16073 AN: 151920 Hom.: 981 Cov.: 32 AF XY: 0.112 AC XY: 8311 AN XY: 74230

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0930

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0907 Hom.: 123

Bravo AF: 0.108

Asia WGS AF: 0.130 AC: 449 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.0
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3767028; hg19: chr1-78408536; COSMIC: COSV53933148; COSMIC: COSV53933148;