rs74642088

Variant names:

• chr11-9847040-G-A
• rs74642088
• NM_030962.4:c.2850C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001386339.1(SBF2):​c.2850C>T​(p.Ile950Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,772 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (65 hom.)
• Consequence: SBF2 NM_001386339.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.857
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics

ENSG00000255476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 11-9847040-G-A is Benign according to our data. Variant chr11-9847040-G-A is described in ClinVar as Benign. ClinVar VariationId is 306592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386339.1. 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
	SBF2	NM_030962.4	MANE Select	c.2850C>T	p.Ile950Ile	synonymous	Exon 23 of 40	NP_112224.1
	SBF2	NM_001386339.1		c.2850C>T	p.Ile950Ile	synonymous	Exon 23 of 41	NP_001373268.1
	SBF2	NM_001424318.1		c.2886C>T	p.Ile962Ile	synonymous	Exon 24 of 41	NP_001411247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.2850C>T	p.Ile950Ile	synonymous	Exon 23 of 40	ENSP00000256190.8
	SBF2	ENST00000533770.6	TSL:1	c.2850C>T	p.Ile950Ile	synonymous	Exon 23 of 26	ENSP00000509247.1
	ENSG00000255476	ENST00000533659.1	TSL:1	n.134+7764G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2295 AN: 152134 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00465 AC: 1170 AN: 251344 AF XY: 0.00354

Gnomad AFR exome AF: 0.0600

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00182 AC: 2660 AN: 1461520 Hom.: 65 Cov.: 31 AF XY: 0.00165 AC XY: 1200 AN XY: 727068

African (AFR) AF: 0.0576 AC: 1928 AN: 33468

American (AMR) AF: 0.00360 AC: 161 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00746 AC: 43 AN: 5766

European-Non Finnish (NFE) AF: 0.000240 AC: 267 AN: 1111690

Other (OTH) AF: 0.00392 AC: 237 AN: 60384

GnomAD4 genome AF: 0.0151 AC: 2297 AN: 152252 Hom.: 61 Cov.: 32 AF XY: 0.0140 AC XY: 1044 AN XY: 74446

African (AFR) AF: 0.0520 AC: 2160 AN: 41538

American (AMR) AF: 0.00491 AC: 75 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68024

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.00719 Hom.: 24

Bravo AF: 0.0176

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000711

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Charcot-Marie-Tooth disease type 4B2 (2)
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.3
DANN	Benign	0.78
PhyloP100		0.86
Mutation Taster		=76/24	polymorphism

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: rs74642088; hg19: chr11-9868587;