dbSNP rs61744747: SUN1:p.Arg681Arg (chr7-869411-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001130965.3(SUN1):c.2043G>A(p.Arg681Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,780 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 58 hom., cov: 32)

Exomes 𝑓: 0.014 ( 673 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0520

Publications

9 publications found

Variant links:

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

SUN1 links:

LOC124901568 (HGNC:):

LOC124901568 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.035).

BP6

Variant 7-869411-G-A is Benign according to our data. Variant chr7-869411-G-A is described in ClinVar as [Benign]. Clinvar id is 461646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.2043G>A	p.Arg681Arg	synonymous_variant	Exon 17 of 19	ENST00000401592.6	NP_001124437.1	O94901-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 link	c.2043G>A	p.Arg681Arg	synonymous_variant	Exon 17 of 19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2045

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0270

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0223

AC:

5565

AN:

249268

AF XY:

0.0226

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.149

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.00889

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.0135

AC:

19754

AN:

1461656

Hom.:

673

Cov.:

AF XY:

0.0142

AC XY:

10350

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00131

AC:

AN:

33480

American (AMR)

AF:

0.00320

AC:

143

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0178

AC:

466

AN:

26122

East Asian (EAS)

AF:

0.152

AC:

6027

AN:

39694

South Asian (SAS)

AF:

0.0277

AC:

2389

AN:

86258

European-Finnish (FIN)

AF:

0.0275

AC:

1469

AN:

53390

Middle Eastern (MID)

AF:

0.0328

AC:

189

AN:

5762

European-Non Finnish (NFE)

AF:

0.00719

AC:

7997

AN:

1111862

Other (OTH)

AF:

0.0171

AC:

1030

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1068

2136

3205

4273

5341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0134

AC:

2043

AN:

152124

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1157

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41486

American (AMR)

AF:

0.00464

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

722

AN:

5150

South Asian (SAS)

AF:

0.0262

AC:

126

AN:

4814

European-Finnish (FIN)

AF:

0.0312

AC:

331

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00910

AC:

619

AN:

67990

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

105

211

316

422

527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SUN1-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.5

(source)

DANN

Benign

0.48

PhyloP100

-0.052

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over