chr22-45362878-T-C

Variant names:

• chr22-45362878-T-C
• rs719925
• NM_148674.5:c.2562+7A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148674.5(SMC1B):​c.2562+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,576,770 control chromosomes in the GnomAD database, including 194,532 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (13747 hom., cov: 32)
  • Exomes 𝑓: 0.50 (180785 hom.)
• Consequence: SMC1B NM_148674.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002911
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC1B	NM_148674.5	c.2562+7A>G		splice_region_variant, intron_variant	Intron 16 of 24	ENST00000357450.9	NP_683515.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC1B	ENST00000357450.9	c.2562+7A>G		splice_region_variant, intron_variant	Intron 16 of 24	5	NM_148674.5	ENSP00000350036.4
SMC1B	ENST00000404354.3	c.2562+7A>G		splice_region_variant, intron_variant	Intron 16 of 22	1		ENSP00000385902.3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59399 AN: 151968 Hom.: 13745 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.404

GnomAD3 exomes AF: 0.439 AC: 98656 AN: 224848 Hom.: 23415 AF XY: 0.439 AC XY: 53747 AN XY: 122466

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.290

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.513

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.495 AC: 705528 AN: 1424686 Hom.: 180785 Cov.: 29 AF XY: 0.493 AC XY: 349430 AN XY: 709446

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.391 AC: 59410 AN: 152084 Hom.: 13747 Cov.: 32 AF XY: 0.386 AC XY: 28668 AN XY: 74322

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.399

Alfa AF: 0.491 Hom.: 30564

Bravo AF: 0.379

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs719925; hg19: chr22-45758758; COSMIC: COSV62529860;