Variant 22-45354086-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_148674.5(SMC1B):c.3165C>G(p.Phe1055Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,600,426 control chromosomes in the GnomAD database, including 2,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 237 hom., cov: 29)

Exomes 𝑓: 0.056 ( 2654 hom. )

Consequence

SMC1B
NM_148674.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.19

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]

SMC1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002321452).

BP6

Variant 22-45354086-G-C is Benign according to our data. Variant chr22-45354086-G-C is described in ClinVar as [Benign]. Clinvar id is 1253849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC1B	NM_148674.5 linkuse as main transcript	c.3165C>G	p.Phe1055Leu	missense_variant	21/25	ENST00000357450.9	NP_683515.4	Q8NDV3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC1B	ENST00000357450.9 linkuse as main transcript	c.3165C>G	p.Phe1055Leu	missense_variant	21/25	5	NM_148674.5	ENSP00000350036.4		Q8NDV3-3
SMC1B	ENST00000404354.3 linkuse as main transcript	c.3165C>G	p.Phe1055Leu	missense_variant	21/23	1		ENSP00000385902.3		Q8NDV3-2

Frequencies

GnomAD3 genomes

AF:

0.0472

AC:

7165

AN:

151648

Hom.:

238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0272

Gnomad SAS

AF:

0.0543

Gnomad FIN

AF:

0.0264

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0563

GnomAD3 exomes

AF:

0.0580

AC:

13680

AN:

235830

Hom.:

556

AF XY:

0.0569

AC XY:

7301

AN XY:

128340

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0241

Gnomad SAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0657

GnomAD4 exome

AF:

0.0559

AC:

80934

AN:

1448660

Hom.:

2654

Cov.:

AF XY:

0.0559

AC XY:

40286

AN XY:

720480

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.0317

Gnomad4 SAS exome

AF:

0.0508

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.0561

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0472

AC:

7165

AN:

151766

Hom.:

237

Cov.:

AF XY:

0.0473

AC XY:

3506

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.0275

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0264

Gnomad4 NFE

AF:

0.0564

Gnomad4 OTH

AF:

0.0566

Alfa

AF:

0.0527

Hom.:

215

Bravo

AF:

0.0499

TwinsUK

AF:

0.0537

AC:

199

ALSPAC

AF:

0.0571

AC:

220

ESP6500AA

AF:

0.0137

AC:

ESP6500EA

AF:

0.0579

AC:

475

ExAC

AF:

0.0552

AC:

6670

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30679340) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.12

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.90

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.61

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.4

D;D

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.27

MutPred

0.41

Gain of MoRF binding (P = 0.1299);Gain of MoRF binding (P = 0.1299);

MPC

1.0

ClinPred

0.031

GERP RS

2.3

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over