rs2645029

Variant names:

• chr11-9790689-G-A
• rs2645029
• NM_030962.4:c.4571-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-9790689-G-A
• chr11-9790689-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030962.4(SBF2):​c.4571-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 1,566,904 control chromosomes in the GnomAD database, including 605,599 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58356 hom., cov: 32)
  • Exomes 𝑓: 0.88 (547243 hom.)
• Consequence: SBF2 NM_030962.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001848
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.842
• Publications: 11 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-AS1 (HGNC:27438): (SBF2 antisense RNA 1)

LOC105369149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-9790689-G-A is Benign according to our data. Variant chr11-9790689-G-A is described in ClinVar as Benign. ClinVar VariationId is 261940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	NM_030962.4	MANE Select	c.4571-6C>T		splice_region intron	N/A	NP_112224.1
	SBF2	NM_001386339.1		c.4667-6C>T		splice_region intron	N/A	NP_001373268.1
	SBF2	NM_001424318.1		c.4607-6C>T		splice_region intron	N/A	NP_001411247.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF2	ENST00000256190.13	TSL:1 MANE Select	c.4571-6C>T		splice_region intron	N/A	ENSP00000256190.8
	SBF2	ENST00000689128.1		c.4667-6C>T		splice_region intron	N/A	ENSP00000509587.1
	SBF2	ENST00000675281.2		c.4646-6C>T		splice_region intron	N/A	ENSP00000502491.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132911 AN: 152120 Hom.: 58327 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.862

GnomAD2 exomes AF: 0.861 AC: 210536 AN: 244590 AF XY: 0.858

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.865

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 0.686

Gnomad FIN exome AF: 0.948

Gnomad NFE exome AF: 0.894

Gnomad OTH exome AF: 0.876

GnomAD4 exome AF: 0.878 AC: 1241731 AN: 1414666 Hom.: 547243 Cov.: 28 AF XY: 0.875 AC XY: 617068 AN XY: 705514

African (AFR) AF: 0.850 AC: 27432 AN: 32262

American (AMR) AF: 0.867 AC: 37681 AN: 43444

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 23415 AN: 25738

East Asian (EAS) AF: 0.684 AC: 26932 AN: 39376

South Asian (SAS) AF: 0.757 AC: 62860 AN: 82992

European-Finnish (FIN) AF: 0.946 AC: 50102 AN: 52970

Middle Eastern (MID) AF: 0.846 AC: 4773 AN: 5642

European-Non Finnish (NFE) AF: 0.892 AC: 957859 AN: 1073346

Other (OTH) AF: 0.860 AC: 50677 AN: 58896

GnomAD4 genome AF: 0.874 AC: 132993 AN: 152238 Hom.: 58356 Cov.: 32 AF XY: 0.872 AC XY: 64946 AN XY: 74438

African (AFR) AF: 0.854 AC: 35432 AN: 41508

American (AMR) AF: 0.880 AC: 13470 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3191 AN: 3470

East Asian (EAS) AF: 0.680 AC: 3520 AN: 5174

South Asian (SAS) AF: 0.741 AC: 3579 AN: 4830

European-Finnish (FIN) AF: 0.953 AC: 10103 AN: 10604

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.894 AC: 60823 AN: 68030

Other (OTH) AF: 0.859 AC: 1817 AN: 2116

Alfa AF: 0.887 Hom.: 27675

Bravo AF: 0.868

Asia WGS AF: 0.693 AC: 2411 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Charcot-Marie-Tooth disease type 4B2 (3)
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		0.84
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000018
dbscSNV1_RF	Benign	0.0
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: rs2645029; hg19: chr11-9812236; COSMIC: COSV56301638; COSMIC: COSV56301638;