rs942434

Positions:

• chr10-7195045-C-T

Variant summary

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

The NM_001387889.1(SFMBT2):​c.1698+2503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,100 control chromosomes in the GnomAD database, including 7,368 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 0.29 (7368 hom., cov: 33)
• Consequence: SFMBT2 NM_001387889.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFMBT2	NM_001387889.1	c.1698+2503G>A		intron_variant		ENST00000397167.6	NP_001374818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFMBT2	ENST00000397167.6	c.1698+2503G>A		intron_variant		5	NM_001387889.1	ENSP00000380353	P4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43621 AN: 151982 Hom.: 7375 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.287 AC: 43602 AN: 152100 Hom.: 7368 Cov.: 33 AF XY: 0.293 AC XY: 21752 AN XY: 74342

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.336

Alfa AF: 0.313 Hom.: 1694

Bravo AF: 0.263

Asia WGS AF: 0.329 AC: 1141 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	0.0070
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs942434; hg19: chr10-7237007; COSMIC: COSV62811773;