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GeneBe

22-45345483-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_148674.5(SMC1B):c.3582C>T(p.Asp1194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,613,120 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 11 hom. )

Consequence

SMC1B
NM_148674.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0660
Variant links:
Genes affected
SMC1B (HGNC:11112): (structural maintenance of chromosomes 1B) SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-45345483-G-A is Benign according to our data. Variant chr22-45345483-G-A is described in ClinVar as [Benign]. Clinvar id is 711091.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.066 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00747 (1138/152274) while in subpopulation AFR AF= 0.0257 (1068/41528). AF 95% confidence interval is 0.0244. There are 12 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1132 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMC1BNM_148674.5 linkuse as main transcriptc.3582C>T p.Asp1194= synonymous_variant 24/25 ENST00000357450.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMC1BENST00000357450.9 linkuse as main transcriptc.3582C>T p.Asp1194= synonymous_variant 24/255 NM_148674.5 P1
SMC1BENST00000404354.3 linkuse as main transcriptc.3360C>T p.Asp1120= synonymous_variant 22/231

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00744
AC:
1132
AN:
152156
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0256
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00269
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00204
AC:
508
AN:
249426
Hom.:
2
AF XY:
0.00167
AC XY:
226
AN XY:
135308
show subpopulations
Gnomad AFR exome
AF:
0.0268
Gnomad AMR exome
AF:
0.000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00284
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000186
Gnomad NFE exome
AF:
0.0000442
Gnomad OTH exome
AF:
0.000495
GnomAD4 exome
AF:
0.000797
AC:
1165
AN:
1460846
Hom.:
11
Cov.:
29
AF XY:
0.000677
AC XY:
492
AN XY:
726792
show subpopulations
Gnomad4 AFR exome
AF:
0.0259
Gnomad4 AMR exome
AF:
0.000850
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00333
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.00149
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00747
AC:
1138
AN:
152274
Hom.:
12
Cov.:
32
AF XY:
0.00712
AC XY:
530
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0257
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00270
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00296
Hom.:
3
Bravo
AF:
0.00822
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
0.097
Dann
Benign
0.88

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9626312; hg19: chr22-45741364; COSMIC: COSV53416273; COSMIC: COSV53416273; API