1-77888900-G-T

Position:

• chr1-77888900-G-T

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.-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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.467

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)

ACMG classification

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
NEXN	NM_144573.4	c.-53+141G>T		intron_variant		ENST00000334785.12
NEXN-AS1	NR_103535.1	n.441C>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEXN	ENST00000334785.12	c.-53+141G>T		intron_variant		1	NM_144573.4	P3
NEXN-AS1	ENST00000421331.1	n.441C>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42167 AN: 151978 Hom.: 6192 Cov.: 32

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

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

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

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 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

Other links and lift over

dbSNP: rs9726525; hg19: chr1-78354585;