Variant 22-45344581-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_148674.5(SMC1B):c.3683G>C(p.Ser1228Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,972 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 28 hom. )

Consequence

SMC1B
NM_148674.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.181

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=0.0028643906).

BP6

Variant 22-45344581-C-G is Benign according to our data. Variant chr22-45344581-C-G is described in ClinVar as [Benign]. Clinvar id is 728760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00116 (176/152338) while in subpopulation EAS AF= 0.0299 (155/5188). AF 95% confidence interval is 0.026. There are 1 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC1B	NM_148674.5 linkuse as main transcript	c.3683G>C	p.Ser1228Thr	missense_variant	25/25	ENST00000357450.9	NP_683515.4	Q8NDV3-3
SMC1B	NM_001291501.2 linkuse as main transcript	c.3461G>C	p.Ser1154Thr	missense_variant	23/23		NP_001278430.1	Q8NDV3-2
SMC1B	XM_011530144.3 linkuse as main transcript	c.3560G>C	p.Ser1187Thr	missense_variant	25/25		XP_011528446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC1B	ENST00000357450.9 linkuse as main transcript	c.3683G>C	p.Ser1228Thr	missense_variant	25/25	5	NM_148674.5	ENSP00000350036.4		Q8NDV3-3
SMC1B	ENST00000404354.3 linkuse as main transcript	c.3461G>C	p.Ser1154Thr	missense_variant	23/23	1		ENSP00000385902.3		Q8NDV3-2

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0296

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00213

AC:

530

AN:

249102

Hom.:

AF XY:

0.00210

AC XY:

284

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.00102

AC:

1493

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

772

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0332

Gnomad4 SAS exome

AF:

0.000603

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00116

AC:

176

AN:

152338

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0299

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00123

ExAC

AF:

0.00221

AC:

267

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.37

DANN

Benign

0.90

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.49

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.093

Sift

Benign

0.12

T;D

Sift4G

Benign

0.50

T;T

Vest4

0.068

MVP

0.31

MPC

0.26

ClinPred

0.015

GERP RS

1.9

gMVP

0.27

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.

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