12-131722044-T-C

Variant names:

• chr12-131722044-T-C
• rs3782288
• NM_004592.4:c.606+2505T>C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFSWAP	NM_004592.4	c.606+2505T>C		intron_variant	Intron 4 of 17	ENST00000261674.9	NP_004583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9	c.606+2505T>C		intron_variant	Intron 4 of 17	1	NM_004592.4	ENSP00000261674.4

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

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.164

Alfa AF: 0.126 Hom.: 178

Bravo AF: 0.142

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.63

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: rs3782288; hg19: chr12-132206589;