22-45371533-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_148674.5(SMC1B):c.2251T>C(p.Leu751=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,599,290 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (132 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (110 hom.)
• Consequence: SMC1B NM_148674.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.473

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 22-45371533-A-G is Benign according to our data. Variant chr22-45371533-A-G is described in ClinVar as [Benign]. Clinvar id is 781635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.473 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC1B	NM_148674.5	c.2251T>C	p.Leu751=	synonymous_variant	14/25	ENST00000357450.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC1B	ENST00000357450.9	c.2251T>C	p.Leu751=	synonymous_variant	14/25	5	NM_148674.5	P1
SMC1B	ENST00000404354.3	c.2251T>C	p.Leu751=	synonymous_variant	14/23	1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3621 AN: 152146 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00601 AC: 1435 AN: 238654 Hom.: 49 AF XY: 0.00431 AC XY: 558 AN XY: 129326

Gnomad AFR exome AF: 0.0815

Gnomad AMR exome AF: 0.00357

Gnomad ASJ exome AF: 0.00449

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000147

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000253

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00231 AC: 3340 AN: 1447026 Hom.: 110 Cov.: 32 AF XY: 0.00200 AC XY: 1437 AN XY: 718942

Gnomad4 AFR exome AF: 0.0781

Gnomad4 AMR exome AF: 0.00414

Gnomad4 ASJ exome AF: 0.00457

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000195

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.0239 AC: 3634 AN: 152264 Hom.: 132 Cov.: 32 AF XY: 0.0228 AC XY: 1700 AN XY: 74452

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.0103 Hom.: 32

Bravo AF: 0.0268

Asia WGS AF: 0.00433 AC: 16 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	2.6
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs75007763; hg19: chr22-45767413;