22-45373365-A-G

Variant names:

• chr22-45373365-A-G
• rs136575
• NM_148674.5:c.2059-1073T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148674.5(SMC1B):​c.2059-1073T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,148 control chromosomes in the GnomAD database, including 32,078 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 0.62 (32078 hom., cov: 32)
• Consequence: SMC1B NM_148674.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 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.2059-1073T>C		intron	N/A	NP_683515.4
	SMC1B	NM_001291501.2		c.2059-1073T>C		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.2059-1073T>C		intron	N/A	ENSP00000350036.4
	SMC1B	ENST00000404354.3	TSL:1	c.2059-1073T>C		intron	N/A	ENSP00000385902.3

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94786 AN: 152028 Hom.: 32028 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.624 AC: 94894 AN: 152148 Hom.: 32078 Cov.: 32 AF XY: 0.629 AC XY: 46745 AN XY: 74364

African (AFR) AF: 0.895 AC: 37162 AN: 41534

American (AMR) AF: 0.573 AC: 8751 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3544 AN: 5178

South Asian (SAS) AF: 0.680 AC: 3278 AN: 4824

European-Finnish (FIN) AF: 0.548 AC: 5787 AN: 10564

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32546 AN: 67984

Other (OTH) AF: 0.613 AC: 1292 AN: 2108

Alfa AF: 0.565 Hom.: 4509

Bravo AF: 0.636

Asia WGS AF: 0.744 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.71
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: rs136575; hg19: chr22-45769245;