dbSNP rs3747238: SMC1B:c.*341G>A (chr22-45344215-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_148674.5(SMC1B):c.*341G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 162,354 control chromosomes in the GnomAD database, including 15,883 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 0.40 ( 14635 hom., cov: 34)

Exomes 𝑓: 0.49 ( 1248 hom. )

Consequence

SMC1B
NM_148674.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.882

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

gonadal dysgenesis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SMC1B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_148674.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148674.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1B	NM_148674.5	MANE Select	c.*341G>A		3_prime_UTR	Exon 25 of 25	NP_683515.4
	SMC1B	NM_001291501.2		c.*341G>A		3_prime_UTR	Exon 23 of 23	NP_001278430.1	Q8NDV3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMC1B	ENST00000357450.9	TSL:5 MANE Select	c.*341G>A	3_prime_UTR	Exon 25 of 25	ENSP00000350036.4	Q8NDV3-3
SMC1B	ENST00000877413.1		c.*341G>A	3_prime_UTR	Exon 23 of 23	ENSP00000547472.1
SMC1B	ENST00000923332.1		c.*341G>A	3_prime_UTR	Exon 21 of 21	ENSP00000593391.1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60235

AN:

152054

Hom.:

14635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.442

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.488

AC:

4971

AN:

10182

Hom.:

1248

Cov.:

AF XY:

0.496

AC XY:

2604

AN XY:

5248

show subpopulations

African (AFR)

AF:

0.118

AC:

AN:

422

American (AMR)

AF:

0.448

AC:

145

AN:

324

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

224

AN:

468

East Asian (EAS)

AF:

0.436

AC:

251

AN:

576

South Asian (SAS)

AF:

0.261

AC:

AN:

142

European-Finnish (FIN)

AF:

0.464

AC:

168

AN:

362

Middle Eastern (MID)

AF:

0.537

AC:

AN:

European-Non Finnish (NFE)

AF:

0.528

AC:

3739

AN:

7088

Other (OTH)

AF:

0.440

AC:

328

AN:

746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.396

AC:

60242

AN:

152172

Hom.:

14635

Cov.:

AF XY:

0.390

AC XY:

29030

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.111

AC:

4602

AN:

41534

American (AMR)

AF:

0.443

AC:

6766

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1716

AN:

3468

East Asian (EAS)

AF:

0.337

AC:

1748

AN:

5184

South Asian (SAS)

AF:

0.328

AC:

1584

AN:

4826

European-Finnish (FIN)

AF:

0.467

AC:

4944

AN:

10576

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37440

AN:

67988

Other (OTH)

AF:

0.408

AC:

861

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1620

3240

4861

6481

8101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.493

Hom.:

14818

Bravo

AF:

0.385

Asia WGS

AF:

0.264

AC:

916

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.75

(source)

DANN

Benign

0.29

PhyloP100

-0.88

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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