1-77917475-AT-A

Variant names:

• chr1-77917475-AT-A
• rs112597766
• NM_144573.4:c.28-85delT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy 1CC

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy 20

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NEXN	NM_144573.4	c.28-85delT		intron_variant	Intron 2 of 12	ENST00000334785.12	NP_653174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12	c.28-90delT		intron_variant	Intron 2 of 12	1	NM_144573.4	ENSP00000333938.7
NEXN	ENST00000401035.7	c.28-484delT		intron_variant	Intron 2 of 8	1		ENSP00000383814.3
NEXN	ENST00000330010.12	c.28-484delT		intron_variant	Intron 2 of 11	2		ENSP00000327363.8
NEXN	ENST00000440324.5	c.28-90delT		intron_variant	Intron 2 of 9	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

African (AFR) AF: 0.229 AC: 4260 AN: 18622

American (AMR) AF: 0.0416 AC: 1246 AN: 29924

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 1819 AN: 20458

East Asian (EAS) AF: 0.0000306 AC: 1 AN: 32722

South Asian (SAS) AF: 0.0290 AC: 1792 AN: 61770

European-Finnish (FIN) AF: 0.0175 AC: 819 AN: 46838

Middle Eastern (MID) AF: 0.113 AC: 397 AN: 3506

European-Non Finnish (NFE) AF: 0.0400 AC: 21627 AN: 540830

Other (OTH) AF: 0.0580 AC: 2177 AN: 37510

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

African (AFR) AF: 0.227 AC: 9401 AN: 41478

American (AMR) AF: 0.0602 AC: 920 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 319 AN: 3468

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.0167 AC: 177 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2913 AN: 67998

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

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

Sep 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112597766; hg19: chr1-78383160;