chr1-77888795-T-G

Position:

• chr1-77888795-T-G

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.-53+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 142,702 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (38 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: NEXN NM_144573.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.898

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-77888795-T-G is Benign according to our data. Variant chr1-77888795-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1194335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEXN	NM_144573.4	c.-53+36T>G		intron_variant		ENST00000334785.12	NP_653174.3
NEXN-AS1	NR_103535.1	n.546A>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEXN	ENST00000334785.12	c.-53+36T>G		intron_variant		1	NM_144573.4	ENSP00000333938	P3
NEXN-AS1	ENST00000421331.1	n.546A>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2005 AN: 141942 Hom.: 37 Cov.: 31

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000225

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000219

Gnomad OTH AF: 0.00920

GnomAD4 exome AF: 0.00148 AC: 1 AN: 676 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 420

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0142 AC: 2012 AN: 142026 Hom.: 38 Cov.: 31 AF XY: 0.0139 AC XY: 962 AN XY: 69280

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.00471

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000225

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000219

Gnomad4 OTH AF: 0.00911

Alfa AF: 0.0137 Hom.: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.37

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: rs147230680; hg19: chr1-78354480;