10-7273352-T-C

Variant names:

• chr10-7273352-T-C
• rs10905146
• NM_001387889.1:c.870+3540A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387889.1(SFMBT2):​c.870+3540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,830 control chromosomes in the GnomAD database, including 30,494 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 0.63 (30494 hom., cov: 33)
• Consequence: SFMBT2 NM_001387889.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFMBT2	NM_001387889.1	MANE Select	c.870+3540A>G		intron	N/A	NP_001374818.1	Q5VUG0
	SFMBT2	NM_001018039.1		c.870+3540A>G		intron	N/A	NP_001018049.1	Q5VUG0
	SFMBT2	NM_001029880.3		c.870+3540A>G		intron	N/A	NP_001025051.1	Q5VUG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFMBT2	ENST00000397167.6	TSL:5 MANE Select	c.870+3540A>G		intron	N/A	ENSP00000380353.1	Q5VUG0
	SFMBT2	ENST00000361972.8	TSL:1	c.870+3540A>G		intron	N/A	ENSP00000355109.4	Q5VUG0
	SFMBT2	ENST00000673876.1		c.867+3540A>G		intron	N/A	ENSP00000501299.1	A0A669KBL2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95624 AN: 151712 Hom.: 30469 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.630 AC: 95704 AN: 151830 Hom.: 30494 Cov.: 33 AF XY: 0.632 AC XY: 46877 AN XY: 74180

African (AFR) AF: 0.683 AC: 28244 AN: 41380

American (AMR) AF: 0.681 AC: 10391 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4090 AN: 5164

South Asian (SAS) AF: 0.405 AC: 1949 AN: 4816

European-Finnish (FIN) AF: 0.669 AC: 7025 AN: 10496

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40363 AN: 67924

Other (OTH) AF: 0.590 AC: 1243 AN: 2108

Alfa AF: 0.613 Hom.: 6529

Bravo AF: 0.641

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.47
Mutation Taster		=100/0	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: rs10905146; hg19: chr10-7315314;