12-131775757-T-C

Variant names:

• chr12-131775757-T-C
• rs755437
• NM_004592.4:c.2143-2308T>C

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SFSWAP	NM_004592.4	c.2143-2308T>C		intron_variant	Intron 13 of 17	ENST00000261674.9	NP_004583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9	c.2143-2308T>C		intron_variant	Intron 13 of 17	1	NM_004592.4	ENSP00000261674.4

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

African (AFR) AF: 0.222 AC: 9184 AN: 41438

American (AMR) AF: 0.417 AC: 6358 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2284 AN: 5162

South Asian (SAS) AF: 0.325 AC: 1558 AN: 4796

European-Finnish (FIN) AF: 0.484 AC: 5092 AN: 10512

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33555 AN: 67926

Other (OTH) AF: 0.388 AC: 815 AN: 2100

Alfa AF: 0.442 Hom.: 2002

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
PhyloP100		-0.32
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: rs755437; hg19: chr12-132260302;