rs79470805

Variant names:

• chr11-9992538-T-C
• rs79470805
• NM_030962.4:c.1173A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_030962.4(SBF2):​c.1173A>G​(p.Ala391Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,610,934 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0091 (108 hom.)
• Consequence: SBF2 NM_030962.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 2.80
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P, Orphanet

ENSG00000286561 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-9992538-T-C is Benign according to our data. Variant chr11-9992538-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 220575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00725 (1103/152182) while in subpopulation SAS AF = 0.0131 (63/4820). AF 95% confidence interval is 0.0105. There are 9 homozygotes in GnomAd4. There are 509 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030962.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.1173A>G	p.Ala391Ala	synonymous	Exon 12 of 40	NP_112224.1	Q86WG5-1
	SBF2	NM_001386339.1		c.1173A>G	p.Ala391Ala	synonymous	Exon 12 of 41	NP_001373268.1	A0A8I5KQ02
	SBF2	NM_001424318.1		c.1209A>G	p.Ala403Ala	synonymous	Exon 13 of 41	NP_001411247.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.1173A>G	p.Ala391Ala	synonymous	Exon 12 of 40	ENSP00000256190.8	Q86WG5-1
	SBF2	ENST00000533770.6	TSL:1	c.1173A>G	p.Ala391Ala	synonymous	Exon 12 of 26	ENSP00000509247.1	Q86WG5-3
	SBF2	ENST00000526353.2	TSL:1	n.1323A>G		non_coding_transcript_exon	Exon 12 of 16

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1102 AN: 152064 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00751 AC: 1870 AN: 249112 AF XY: 0.00828

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00429

Gnomad ASJ exome AF: 0.00830

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.00954

Gnomad OTH exome AF: 0.00938

GnomAD4 exome AF: 0.00909 AC: 13256 AN: 1458752 Hom.: 108 Cov.: 30 AF XY: 0.00941 AC XY: 6828 AN XY: 725494

African (AFR) AF: 0.00204 AC: 68 AN: 33378

American (AMR) AF: 0.00488 AC: 216 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00745 AC: 194 AN: 26034

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39562

South Asian (SAS) AF: 0.0141 AC: 1203 AN: 85524

European-Finnish (FIN) AF: 0.00414 AC: 221 AN: 53360

Middle Eastern (MID) AF: 0.0454 AC: 261 AN: 5750

European-Non Finnish (NFE) AF: 0.00947 AC: 10513 AN: 1110608

Other (OTH) AF: 0.00959 AC: 578 AN: 60248

GnomAD4 genome AF: 0.00725 AC: 1103 AN: 152182 Hom.: 9 Cov.: 32 AF XY: 0.00684 AC XY: 509 AN XY: 74412

African (AFR) AF: 0.00180 AC: 75 AN: 41560

American (AMR) AF: 0.00623 AC: 95 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4820

European-Finnish (FIN) AF: 0.00359 AC: 38 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 752 AN: 67978

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00791 Hom.: 9

Bravo AF: 0.00725

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs79470805; hg19: chr11-10014085; COSMIC: COSV99815491; COSMIC: COSV99815491;