22-45359968-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_148674.5(SMC1B):c.2709-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,609,880 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (43 hom.)
• Consequence: SMC1B NM_148674.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003568
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.354

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-45359968-C-T is Benign according to our data. Variant chr22-45359968-C-T is described in ClinVar as [Benign]. Clinvar id is 781622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMC1B	NM_148674.5	c.2709-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000357450.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMC1B	ENST00000357450.9	c.2709-10G>A		splice_polypyrimidine_tract_variant, intron_variant		5	NM_148674.5	P1
SMC1B	ENST00000404354.3	c.2709-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2262 AN: 152176 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00355 AC: 879 AN: 247750 Hom.: 18 AF XY: 0.00257 AC XY: 346 AN XY: 134468

Gnomad AFR exome AF: 0.0513

Gnomad AMR exome AF: 0.00210

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000801

Gnomad OTH exome AF: 0.000832

GnomAD4 exome AF: 0.00138 AC: 2005 AN: 1457586 Hom.: 43 Cov.: 30 AF XY: 0.00115 AC XY: 834 AN XY: 724954

Gnomad4 AFR exome AF: 0.0494

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000582

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000649

Gnomad4 OTH exome AF: 0.00271

GnomAD4 genome AF: 0.0149 AC: 2273 AN: 152294 Hom.: 62 Cov.: 33 AF XY: 0.0140 AC XY: 1040 AN XY: 74476

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0104 Hom.: 11

Bravo AF: 0.0167

Asia WGS AF: 0.00346 AC: 13 AN: 3478

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

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.030		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: rs73442488; hg19: chr22-45755848;