22-45378388-C-T

Position:

• chr22-45378388-C-T

Variant summary

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

The NM_148674.5(SMC1B):​c.2058+5079G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 152,044 control chromosomes in the GnomAD database, including 398 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 0.060 (398 hom., cov: 32)
• Consequence: SMC1B NM_148674.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMC1B	NM_148674.5	c.2058+5079G>A		intron_variant		ENST00000357450.9	NP_683515.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMC1B	ENST00000357450.9	c.2058+5079G>A		intron_variant		5	NM_148674.5	ENSP00000350036	P1
SMC1B	ENST00000404354.3	c.2058+5079G>A		intron_variant		1		ENSP00000385902

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9086 AN: 151926 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0369

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0597 AC: 9082 AN: 152044 Hom.: 398 Cov.: 32 AF XY: 0.0574 AC XY: 4262 AN XY: 74310

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0641

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0371

Gnomad4 FIN AF: 0.0876

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0750 Hom.: 203

Bravo AF: 0.0571

Asia WGS AF: 0.0170 AC: 58 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.62

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: rs17639579; hg19: chr22-45774268;