chr11-9748015-C-T

Variant names:

• chr11-9748015-C-T
• rs415895
• NM_015055.4:c.1513C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015055.4(SWAP70):​c.1513C>T​(p.Gln505*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SWAP70 NM_015055.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 60 publications found

Genes affected

SWAP70 (HGNC:17070): (switching B cell complex subunit SWAP70) Enables cadherin binding activity. Predicted to be involved in regulation of actin polymerization or depolymerization. Predicted to act upstream of or within isotype switching. Located in actin cytoskeleton; cytoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015055.4. 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
	SWAP70	NM_015055.4	MANE Select	c.1513C>T	p.Gln505*	stop_gained	Exon 10 of 12	NP_055870.2
	SWAP70	NM_001297714.2		c.1339C>T	p.Gln447*	stop_gained	Exon 9 of 11	NP_001284643.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SWAP70	ENST00000318950.11	TSL:1 MANE Select	c.1513C>T	p.Gln505*	stop_gained	Exon 10 of 12	ENSP00000315630.6
	SWAP70	ENST00000447399.6	TSL:2	c.1339C>T	p.Gln447*	stop_gained	Exon 9 of 11	ENSP00000399056.2
	SWAP70	ENST00000534562.1	TSL:5	n.*699-2269C>T		intron	N/A	ENSP00000433824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Uncertain	0.97	D
PhyloP100		4.5
Vest4		0.75
GERP RS		5.7
Mutation Taster		=19/181	disease causing (fs/PTC)

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: rs415895; hg19: chr11-9769562;