chr22-45368994-T-C

Variant names:

• chr22-45368994-T-C
• rs136564
• NM_148674.5:c.2420+960A>G

Variant summary

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

The NM_148674.5(SMC1B):​c.2420+960A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,210 control chromosomes in the GnomAD database, including 1,248 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 0.12 (1248 hom., cov: 32)
• Consequence: SMC1B NM_148674.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 23 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMC1B	NM_148674.5	c.2420+960A>G		intron_variant	Intron 15 of 24	ENST00000357450.9	NP_683515.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMC1B	ENST00000357450.9	c.2420+960A>G		intron_variant	Intron 15 of 24	5	NM_148674.5	ENSP00000350036.4
SMC1B	ENST00000404354.3	c.2420+960A>G		intron_variant	Intron 15 of 22	1		ENSP00000385902.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17901 AN: 152094 Hom.: 1248 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.118 AC: 17898 AN: 152210 Hom.: 1248 Cov.: 32 AF XY: 0.126 AC XY: 9369 AN XY: 74428

African (AFR) AF: 0.0478 AC: 1985 AN: 41556

American (AMR) AF: 0.124 AC: 1899 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.193 AC: 998 AN: 5180

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2126 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8645 AN: 68012

Other (OTH) AF: 0.129 AC: 272 AN: 2110

Alfa AF: 0.114 Hom.: 633

Bravo AF: 0.108

Asia WGS AF: 0.216 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		-0.44
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: rs136564; hg19: chr22-45764874;