rs6743259

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142286.2(SMC6):​c.345-2095C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,196 control chromosomes in the GnomAD database, including 907 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.085 ( 907 hom., cov: 32)

Consequence

SMC6
NM_001142286.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Publications

3 publications found
Variant links:
Genes affected
SMC6 (HGNC:20466): (structural maintenance of chromosomes 6) Enables ubiquitin protein ligase binding activity. Involved in several processes, including cellular senescence; positive regulation of chromosome segregation; and telomere maintenance via recombination. Located in chromosome and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMC6NM_001142286.2 linkc.345-2095C>G intron_variant Intron 5 of 27 ENST00000448223.7 NP_001135758.1 Q96SB8-1A0A2S1ZR87

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMC6ENST00000448223.7 linkc.345-2095C>G intron_variant Intron 5 of 27 1 NM_001142286.2 ENSP00000404092.2 Q96SB8-1

Frequencies

GnomAD3 genomes
AF:
0.0853
AC:
12967
AN:
152078
Hom.:
907
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.192
Gnomad AMI
AF:
0.0614
Gnomad AMR
AF:
0.0570
Gnomad ASJ
AF:
0.0435
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0288
Gnomad FIN
AF:
0.0249
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.0495
Gnomad OTH
AF:
0.0789
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0853
AC:
12986
AN:
152196
Hom.:
907
Cov.:
32
AF XY:
0.0821
AC XY:
6114
AN XY:
74430
show subpopulations
African (AFR)
AF:
0.192
AC:
7965
AN:
41528
American (AMR)
AF:
0.0568
AC:
869
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.0435
AC:
151
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.0290
AC:
140
AN:
4828
European-Finnish (FIN)
AF:
0.0249
AC:
264
AN:
10606
Middle Eastern (MID)
AF:
0.0476
AC:
14
AN:
294
European-Non Finnish (NFE)
AF:
0.0495
AC:
3362
AN:
67966
Other (OTH)
AF:
0.0781
AC:
165
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
595
1189
1784
2378
2973
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
136
272
408
544
680
<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:
0.0716
Hom.:
81
Bravo
AF:
0.0933
Asia WGS
AF:
0.0250
AC:
85
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.6
DANN
Benign
0.68
PhyloP100
0.14
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs6743259; hg19: chr2-17915239; API