1-77916353-A-C

Position:

• chr1-77916353-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.599

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 -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
NEXN	NM_144573.4	c.27+220A>C		intron_variant		ENST00000334785.12	NP_653174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12	c.27+220A>C		intron_variant		1	NM_144573.4	ENSP00000333938	P3
NEXN	ENST00000401035.7	c.27+220A>C		intron_variant		1		ENSP00000383814
NEXN	ENST00000330010.12	c.27+220A>C		intron_variant		2		ENSP00000327363	A1
NEXN	ENST00000440324.5	c.27+220A>C		intron_variant		5		ENSP00000411902

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6755 AN: 152114 Hom.: 230 Cov.: 32

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

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This 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

Other links and lift over

dbSNP: rs74092331; hg19: chr1-78382038;