chr12-131722044-T-C

Variant names:

• chr12-131722044-T-C
• rs3782288
• NM_004592.4:c.606+2505T>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.606+2505T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,184 control chromosomes in the GnomAD database, including 2,227 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 0.15 (2227 hom., cov: 32)
• Consequence: SFSWAP NM_004592.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004592.4. 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
	SFSWAP	NM_004592.4	MANE Select	c.606+2505T>C		intron	N/A	NP_004583.2
	SFSWAP	NM_001261411.2		c.606+2505T>C		intron	N/A	NP_001248340.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFSWAP	ENST00000261674.9	TSL:1 MANE Select	c.606+2505T>C		intron	N/A	ENSP00000261674.4
	SFSWAP	ENST00000541286.5	TSL:1	c.606+2505T>C		intron	N/A	ENSP00000437738.1
	SFSWAP	ENST00000535236.5	TSL:1	n.3940+2505T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22221 AN: 152066 Hom.: 2227 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.146 AC: 22230 AN: 152184 Hom.: 2227 Cov.: 32 AF XY: 0.156 AC XY: 11600 AN XY: 74414

African (AFR) AF: 0.0894 AC: 3712 AN: 41532

American (AMR) AF: 0.182 AC: 2783 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2701 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4816

European-Finnish (FIN) AF: 0.216 AC: 2289 AN: 10586

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8559 AN: 67998

Other (OTH) AF: 0.164 AC: 346 AN: 2116

Alfa AF: 0.124 Hom.: 178

Bravo AF: 0.142

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.63
PhyloP100		0.60
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: rs3782288; hg19: chr12-132206589;