NM_148674.5:c.2058+5079G>A

Variant names:

• chr22-45378388-C-T
• rs17639579
• NM_148674.5:c.2058+5079G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1B	NM_148674.5	MANE Select	c.2058+5079G>A		intron	N/A	NP_683515.4
	SMC1B	NM_001291501.2		c.2058+5079G>A		intron	N/A	NP_001278430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMC1B	ENST00000357450.9	TSL:5 MANE Select	c.2058+5079G>A		intron	N/A	ENSP00000350036.4
	SMC1B	ENST00000404354.3	TSL:1	c.2058+5079G>A		intron	N/A	ENSP00000385902.3

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

African (AFR) AF: 0.0154 AC: 640 AN: 41486

American (AMR) AF: 0.0641 AC: 979 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0371 AC: 179 AN: 4822

European-Finnish (FIN) AF: 0.0876 AC: 924 AN: 10542

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0876 AC: 5956 AN: 67970

Other (OTH) AF: 0.0645 AC: 136 AN: 2108

Alfa AF: 0.0758 Hom.: 226

Bravo AF: 0.0571

Asia WGS AF: 0.0170 AC: 58 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17639579; hg19: chr22-45774268;