rs5771001

Variant names:

• chr22-50456591-C-T
• rs5771001
• NM_002972.4:c.3987G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50456591-C-T
• chr22-50456591-C-A
• chr22-50456591-C-G

Variant summary

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

The NM_002972.4(SBF1):​c.3987G>A​(p.Ala1329Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,543,372 control chromosomes in the GnomAD database, including 43,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4437 hom., cov: 30)
  • Exomes 𝑓: 0.22 (39330 hom.)
• Consequence: SBF1 NM_002972.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.12
• Publications: 19 publications found

Genes affected

SBF1 (HGNC:10542): (SET binding factor 1) This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

SBF1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4B3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 22-50456591-C-T is Benign according to our data. Variant chr22-50456591-C-T is described in ClinVar as Benign. ClinVar VariationId is 258879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002972.4. 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
	SBF1	NM_002972.4	MANE Select	c.3987G>A	p.Ala1329Ala	synonymous	Exon 30 of 41	NP_002963.2	O95248-5
	SBF1	NM_001410794.1		c.3990G>A	p.Ala1330Ala	synonymous	Exon 30 of 41	NP_001397723.1	O95248-4
	SBF1	NM_001365819.1		c.3912G>A	p.Ala1304Ala	synonymous	Exon 29 of 40	NP_001352748.1	O95248-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBF1	ENST00000380817.8	TSL:1 MANE Select	c.3987G>A	p.Ala1329Ala	synonymous	Exon 30 of 41	ENSP00000370196.2	O95248-5
	SBF1	ENST00000931646.1		c.4047G>A	p.Ala1349Ala	synonymous	Exon 30 of 41	ENSP00000601705.1
	SBF1	ENST00000967446.1		c.4008G>A	p.Ala1336Ala	synonymous	Exon 30 of 41	ENSP00000637505.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31911 AN: 151890 Hom.: 4441 Cov.: 30

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.285 AC: 45396 AN: 159552 AF XY: 0.277

Gnomad AFR exome AF: 0.0967

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.712

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.219 AC: 304539 AN: 1391362 Hom.: 39330 Cov.: 40 AF XY: 0.219 AC XY: 150160 AN XY: 686146

African (AFR) AF: 0.0968 AC: 3057 AN: 31582

American (AMR) AF: 0.387 AC: 13553 AN: 34998

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 2996 AN: 22292

East Asian (EAS) AF: 0.701 AC: 26549 AN: 37878

South Asian (SAS) AF: 0.243 AC: 18176 AN: 74882

European-Finnish (FIN) AF: 0.279 AC: 13412 AN: 48122

Middle Eastern (MID) AF: 0.172 AC: 937 AN: 5438

European-Non Finnish (NFE) AF: 0.197 AC: 212961 AN: 1078882

Other (OTH) AF: 0.225 AC: 12898 AN: 57288

GnomAD4 genome AF: 0.210 AC: 31916 AN: 152010 Hom.: 4437 Cov.: 30 AF XY: 0.217 AC XY: 16158 AN XY: 74294

African (AFR) AF: 0.104 AC: 4329 AN: 41478

American (AMR) AF: 0.299 AC: 4558 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3647 AN: 5156

South Asian (SAS) AF: 0.254 AC: 1222 AN: 4818

European-Finnish (FIN) AF: 0.276 AC: 2921 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14080 AN: 67936

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.200 Hom.: 646

Bravo AF: 0.212

Asia WGS AF: 0.395 AC: 1367 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Charcot-Marie-Tooth disease type 4B3 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.6
DANN	Benign	0.62
PhyloP100		1.1
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	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: rs5771001; hg19: chr22-50895020; COSMIC: COSV62365326; COSMIC: COSV62365326;