rs1751658

Positions:

• chr10-7348338-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387889.1(SFMBT2):​c.436+19311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,512,824 control chromosomes in the GnomAD database, including 30,703 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4850 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25853 hom.)
• Consequence: SFMBT2 NM_001387889.1 intron
• Scores: Splicing: ADA: 0.00001992
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

Genes affected

SFMBT2 (HGNC:20256): (Scm like with four mbt domains 2) Enables histone binding activity. Involved in negative regulation of gene expression. Located in aggresome; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902372 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFMBT2	NM_001387889.1	c.436+19311T>C		intron_variant		ENST00000397167.6	NP_001374818.1
LOC124902372	XR_007062049.1	n.16804T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFMBT2	ENST00000397167.6	c.436+19311T>C		intron_variant		5	NM_001387889.1	ENSP00000380353	P4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34753 AN: 151972 Hom.: 4825 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.201

GnomAD3 exomes AF: 0.151 AC: 19610 AN: 129872 Hom.: 1926 AF XY: 0.147 AC XY: 10370 AN XY: 70530

Gnomad AFR exome AF: 0.390

Gnomad AMR exome AF: 0.153

Gnomad ASJ exome AF: 0.0604

Gnomad EAS exome AF: 0.00514

Gnomad SAS exome AF: 0.0741

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.186 AC: 252703 AN: 1360734 Hom.: 25853 Cov.: 29 AF XY: 0.182 AC XY: 121958 AN XY: 670422

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0620

Gnomad4 EAS exome AF: 0.00189

Gnomad4 SAS exome AF: 0.0786

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.229 AC: 34822 AN: 152090 Hom.: 4850 Cov.: 32 AF XY: 0.219 AC XY: 16271 AN XY: 74352

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.199

Alfa AF: 0.205 Hom.: 1779

Bravo AF: 0.237

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
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

Publications

LitVar

Other links and lift over

dbSNP: rs1751658; hg19: chr10-7390300; COSMIC: COSV62818860;