rs3767028

Variant names:

• chr1-77942851-C-G
• rs3767028
• NM_144573.4:c.*22C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-77942851-C-G
• chr1-77942851-C-A
• chr1-77942851-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144573.4(NEXN):​c.*22C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,578,918 control chromosomes in the GnomAD database, including 7,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (981 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6395 hom.)
• Consequence: NEXN NM_144573.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236
• Publications: 8 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: STRONG 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: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-77942851-C-G is Benign according to our data. Variant chr1-77942851-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEXN	NM_144573.4	MANE Select	c.*22C>G		3_prime_UTR	Exon 13 of 13	NP_653174.3	Q0ZGT2-1
	NEXN	NM_001172309.2		c.*22C>G		3_prime_UTR	Exon 12 of 12	NP_001165780.1	Q0ZGT2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEXN	ENST00000334785.12	TSL:1 MANE Select	c.*22C>G		3_prime_UTR	Exon 13 of 13	ENSP00000333938.7	Q0ZGT2-1
	NEXN	ENST00000342754.5	TSL:1	c.1714+33C>G		intron	N/A	ENSP00000343928.5	H7BXY5
	NEXN	ENST00000951152.1		c.*22C>G		3_prime_UTR	Exon 14 of 14	ENSP00000621211.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16035 AN: 151802 Hom.: 974 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.122 AC: 26418 AN: 215808 AF XY: 0.118

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.0868

Gnomad EAS exome AF: 0.0938

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.0850

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.0876 AC: 125063 AN: 1426998 Hom.: 6395 Cov.: 28 AF XY: 0.0880 AC XY: 62434 AN XY: 709358

African (AFR) AF: 0.107 AC: 3372 AN: 31566

American (AMR) AF: 0.231 AC: 9912 AN: 42972

Ashkenazi Jewish (ASJ) AF: 0.0891 AC: 2301 AN: 25826

East Asian (EAS) AF: 0.0821 AC: 3041 AN: 37060

South Asian (SAS) AF: 0.114 AC: 9459 AN: 83108

European-Finnish (FIN) AF: 0.148 AC: 7698 AN: 52032

Middle Eastern (MID) AF: 0.0889 AC: 404 AN: 4542

European-Non Finnish (NFE) AF: 0.0764 AC: 83329 AN: 1090966

Other (OTH) AF: 0.0941 AC: 5547 AN: 58926

GnomAD4 genome AF: 0.106 AC: 16073 AN: 151920 Hom.: 981 Cov.: 32 AF XY: 0.112 AC XY: 8311 AN XY: 74230

African (AFR) AF: 0.105 AC: 4353 AN: 41460

American (AMR) AF: 0.187 AC: 2847 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 322 AN: 3462

East Asian (EAS) AF: 0.0871 AC: 451 AN: 5176

South Asian (SAS) AF: 0.111 AC: 535 AN: 4822

European-Finnish (FIN) AF: 0.171 AC: 1795 AN: 10520

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5390 AN: 67926

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0907 Hom.: 123

Bravo AF: 0.108

Asia WGS AF: 0.130 AC: 449 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3767028; hg19: chr1-78408536; COSMIC: COSV53933148; COSMIC: COSV53933148;