1-77917475-AT-A

Position:

• chr1-77917475-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_144573.4(NEXN):​c.28-85delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 944,344 control chromosomes in the GnomAD database, including 2,535 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (1247 hom., cov: 31)
  • Exomes 𝑓: 0.043 (1288 hom.)
• Consequence: NEXN NM_144573.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.250

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 -10 ACMG points.

• BP6: Variant 1-77917475-AT-A is Benign according to our data. Variant chr1-77917475-AT-A is described in ClinVar as [Benign]. Clinvar id is 1287762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXN	NM_144573.4	c.28-85delT		intron_variant		ENST00000334785.12	NP_653174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12	c.28-85delT		intron_variant		1	NM_144573.4	ENSP00000333938.7
NEXN	ENST00000401035.7	c.28-479delT		intron_variant		1		ENSP00000383814.3
NEXN	ENST00000330010.12	c.28-479delT		intron_variant		2		ENSP00000327363.8
NEXN	ENST00000440324.5	c.28-85delT		intron_variant		5		ENSP00000411902.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14119 AN: 152046 Hom.: 1246 Cov.: 31

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0986

GnomAD4 exome AF: 0.0431 AC: 34138 AN: 792180 Hom.: 1288 AF XY: 0.0417 AC XY: 17194 AN XY: 412402

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.0889

Gnomad4 EAS exome AF: 0.0000306

Gnomad4 SAS exome AF: 0.0290

Gnomad4 FIN exome AF: 0.0175

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0928 AC: 14122 AN: 152164 Hom.: 1247 Cov.: 31 AF XY: 0.0887 AC XY: 6600 AN XY: 74422

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.0161 Hom.: 5

Bravo AF: 0.103

Asia WGS AF: 0.0290 AC: 102 AN: 3472

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

Sep 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs112597766; hg19: chr1-78383160;