Genetic Variant ENST00000457378.6:c.44-42T>C (chr7-832463-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000457378.6(SUN1):c.44-42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,531,254 control chromosomes in the GnomAD database, including 17,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 1956 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15936 hom. )

Consequence

SUN1
ENST00000457378.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.575

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-832463-T-C is Benign according to our data. Variant chr7-832463-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252919.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457378.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SUN1	NM_001367651.1	c.297-6335T>C	intron	N/A	NP_001354580.1
SUN1	NM_001367705.1	c.-20-42T>C	intron	N/A	NP_001354634.1	O94901-9
SUN1	NM_001367678.1	c.-20-42T>C	intron	N/A	NP_001354607.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SUN1	ENST00000457378.6	TSL:1	c.44-42T>C	intron	N/A	ENSP00000395952.2	O94901-7
SUN1	ENST00000916987.1		c.-62T>C	5_prime_UTR	Exon 1 of 21	ENSP00000587046.1
SUN1	ENST00000963179.1		c.-62T>C	5_prime_UTR	Exon 1 of 21	ENSP00000633238.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23312

AN:

152104

Hom.:

1952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0568

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.143

AC:

25884

AN:

181634

AF XY:

0.135

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.000767

Gnomad FIN exome

AF:

0.199

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.146

AC:

200841

AN:

1379032

Hom.:

15936

Cov.:

AF XY:

0.143

AC XY:

97989

AN XY:

684526

show subpopulations

African (AFR)

AF:

0.170

AC:

5363

AN:

31574

American (AMR)

AF:

0.218

AC:

8121

AN:

37210

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2723

AN:

25156

East Asian (EAS)

AF:

0.000727

AC:

AN:

37116

South Asian (SAS)

AF:

0.0634

AC:

5075

AN:

80018

European-Finnish (FIN)

AF:

0.196

AC:

9951

AN:

50682

Middle Eastern (MID)

AF:

0.0783

AC:

442

AN:

5646

European-Non Finnish (NFE)

AF:

0.153

AC:

161369

AN:

1054078

Other (OTH)

AF:

0.135

AC:

7770

AN:

57552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

8372

16744

25117

33489

41861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5668

11336

17004

22672

28340

<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:

0.153

AC:

23336

AN:

152222

Hom.:

1956

Cov.:

AF XY:

0.151

AC XY:

11267

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.172

AC:

7159

AN:

41536

American (AMR)

AF:

0.148

AC:

2266

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5180

South Asian (SAS)

AF:

0.0570

AC:

275

AN:

4824

European-Finnish (FIN)

AF:

0.198

AC:

2103

AN:

10602

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10689

AN:

67996

Other (OTH)

AF:

0.126

AC:

267

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

996

1993

2989

3986

4982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.157

Hom.:

654

Bravo

AF:

0.151

Asia WGS

AF:

0.0410

AC:

143

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.43

(source)

DANN

Benign

0.20

PhyloP100

-0.57

PromoterAI

-0.42

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over