12-131775757-T-C

Position:

• chr12-131775757-T-C

Variant summary

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

The NM_004592.4(SFSWAP):​c.2143-2308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,858 control chromosomes in the GnomAD database, including 13,305 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 0.40 (13305 hom., cov: 31)
• Consequence: SFSWAP NM_004592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

Genes affected

SFSWAP (HGNC:10790): (splicing factor SWAP) This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFSWAP	NM_004592.4	c.2143-2308T>C		intron_variant		ENST00000261674.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFSWAP	ENST00000261674.9	c.2143-2308T>C		intron_variant		1	NM_004592.4	P4

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61020 AN: 151740 Hom.: 13303 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.402 AC: 61030 AN: 151858 Hom.: 13305 Cov.: 31 AF XY: 0.400 AC XY: 29681 AN XY: 74220

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.388

Alfa AF: 0.451 Hom.: 1979

Bravo AF: 0.392

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.20

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: rs755437; hg19: chr12-132260302;