rs1751658

Variant names:

• chr10-7348338-A-G
• rs1751658
• NM_001387889.1:c.436+19311T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387889.1. 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
	SFMBT2	NM_001387889.1	MANE Select	c.436+19311T>C		intron	N/A	NP_001374818.1
	SFMBT2	NM_001018039.1		c.436+19311T>C		intron	N/A	NP_001018049.1
	SFMBT2	NM_001029880.3		c.436+19311T>C		intron	N/A	NP_001025051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFMBT2	ENST00000397167.6	TSL:5 MANE Select	c.436+19311T>C		intron	N/A	ENSP00000380353.1
	SFMBT2	ENST00000361972.8	TSL:1	c.436+19311T>C		intron	N/A	ENSP00000355109.4
	SFMBT2	ENST00000673876.1		c.433+19311T>C		intron	N/A	ENSP00000501299.1

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

GnomAD2 exomes AF: 0.151 AC: 19610 AN: 129872 AF XY: 0.147

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 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

African (AFR) AF: 0.378 AC: 11351 AN: 30008

American (AMR) AF: 0.156 AC: 4641 AN: 29750

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 1510 AN: 24352

East Asian (EAS) AF: 0.00189 AC: 66 AN: 34860

South Asian (SAS) AF: 0.0786 AC: 5804 AN: 73816

European-Finnish (FIN) AF: 0.162 AC: 7671 AN: 47260

Middle Eastern (MID) AF: 0.116 AC: 645 AN: 5568

European-Non Finnish (NFE) AF: 0.200 AC: 211310 AN: 1059024

Other (OTH) AF: 0.173 AC: 9705 AN: 56096

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

African (AFR) AF: 0.387 AC: 16028 AN: 41450

American (AMR) AF: 0.169 AC: 2583 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.0718 AC: 346 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10588

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13472 AN: 67976

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.208 Hom.: 1944

Bravo AF: 0.237

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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