rs115345208

chr11-9790561-T-Cchr11-9790561-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030962.4(SBF2):c.4693A>G(p.Ile1565Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00048 in 1,583,982 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: SBF2 NM_030962.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.20

Genes affected

SBF2 (HGNC:2135): (SET binding factor 2) This gene encodes a pseudophosphatase and member of the myotubularin-related protein family. This gene maps within the CMT4B2 candidate region of chromosome 11p15 and mutations in this gene have been associated with Charcot-Marie-Tooth Disease, type 4B2. [provided by RefSeq, Jul 2008]

SBF2-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

LOC105369149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069927275).
• BP6: Variant 11-9790561-T-C is Benign according to our data. Variant chr11-9790561-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 381819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00264 (402/152326) while in subpopulation AFR AF= 0.00912 (379/41574). AF 95% confidence interval is 0.00836. There are 2 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBF2	NM_030962.4	c.4693A>G	p.Ile1565Val	missense_variant	34/40	ENST00000256190.13
SBF2-AS1	NR_036485.1	n.212-17287T>C		intron_variant, non_coding_transcript_variant
LOC105369149	XR_007062587.1	n.356-308T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBF2	ENST00000256190.13	c.4693A>G	p.Ile1565Val	missense_variant	34/40	1	NM_030962.4	P3
SBF2-AS1	ENST00000663578.1	n.237-17287T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 401 AN: 152208 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000788 AC: 193 AN: 244936 Hom.: 1 AF XY: 0.000636 AC XY: 84 AN XY: 132110

Gnomad AFR exome AF: 0.0107

Gnomad AMR exome AF: 0.000480

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000501

GnomAD4 exome AF: 0.000250 AC: 358 AN: 1431656 Hom.: 2 Cov.: 27 AF XY: 0.000217 AC XY: 155 AN XY: 713046

Gnomad4 AFR exome AF: 0.00820

Gnomad4 AMR exome AF: 0.000576

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000241

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000248

Gnomad4 OTH exome AF: 0.000589

GnomAD4 genome AF: 0.00264 AC: 402 AN: 152326 Hom.: 2 Cov.: 33 AF XY: 0.00247 AC XY: 184 AN XY: 74502

Gnomad4 AFR AF: 0.00912

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000350 Hom.: 1

Bravo AF: 0.00317

ESP6500AA AF: 0.00795 AC: 35

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000981 AC: 119

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 21, 2018

- -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 11, 2021

- -

Charcot-Marie-Tooth disease type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	16
Dann	Benign	0.95
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.72	N
MutationTaster	Benign	0.94	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.13
Sift	Benign	0.33	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.71
MPC		0.15
ClinPred		0.0043	T
GERP RS		3.7
Varity_R		0.032
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs115345208; hg19: chr11-9812108;