11-9748015-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015055.4(SWAP70):​c.1513C>G​(p.Gln505Glu) variant causes a missense change. The variant allele was found at a frequency of 0.635 in 1,613,856 control chromosomes in the GnomAD database, including 328,350 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28864 hom., cov: 32)
  • Exomes 𝑓: 0.64 (299486 hom.)
• Consequence: SWAP70 NM_015055.4 missense
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.058179E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

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>G	p.Gln505Glu	missense	Exon 10 of 12	NP_055870.2
	SWAP70	NM_001297714.2		c.1339C>G	p.Gln447Glu	missense	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>G	p.Gln505Glu	missense	Exon 10 of 12	ENSP00000315630.6
	SWAP70	ENST00000447399.6	TSL:2	c.1339C>G	p.Gln447Glu	missense	Exon 9 of 11	ENSP00000399056.2
	SWAP70	ENST00000534562.1	TSL:5	n.*699-2269C>G		intron	N/A	ENSP00000433824.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92910 AN: 151962 Hom.: 28862 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.649

GnomAD2 exomes AF: 0.624 AC: 156837 AN: 251368 AF XY: 0.625

Gnomad AFR exome AF: 0.520

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.408

Gnomad FIN exome AF: 0.743

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.637 AC: 931377 AN: 1461776 Hom.: 299486 Cov.: 63 AF XY: 0.636 AC XY: 462528 AN XY: 727196

African (AFR) AF: 0.515 AC: 17245 AN: 33478

American (AMR) AF: 0.626 AC: 28005 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 18573 AN: 26134

East Asian (EAS) AF: 0.391 AC: 15523 AN: 39700

South Asian (SAS) AF: 0.544 AC: 46941 AN: 86254

European-Finnish (FIN) AF: 0.740 AC: 39491 AN: 53400

Middle Eastern (MID) AF: 0.725 AC: 4183 AN: 5768

European-Non Finnish (NFE) AF: 0.650 AC: 723079 AN: 1111928

Other (OTH) AF: 0.635 AC: 38337 AN: 60392

GnomAD4 genome AF: 0.611 AC: 92927 AN: 152080 Hom.: 28864 Cov.: 32 AF XY: 0.610 AC XY: 45322 AN XY: 74342

African (AFR) AF: 0.521 AC: 21597 AN: 41448

American (AMR) AF: 0.597 AC: 9123 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2488 AN: 3466

East Asian (EAS) AF: 0.412 AC: 2135 AN: 5180

South Asian (SAS) AF: 0.510 AC: 2458 AN: 4822

European-Finnish (FIN) AF: 0.754 AC: 7969 AN: 10564

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44917 AN: 67994

Other (OTH) AF: 0.649 AC: 1369 AN: 2108

Alfa AF: 0.649 Hom.: 24311

Bravo AF: 0.601

TwinsUK AF: 0.641 AC: 2376

ALSPAC AF: 0.657 AC: 2533

ESP6500AA AF: 0.530 AC: 2332

ESP6500EA AF: 0.669 AC: 5748

ExAC AF: 0.621 AC: 75428

Asia WGS AF: 0.473 AC: 1646 AN: 3478

EpiCase AF: 0.664

EpiControl AF: 0.674

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.12	B
Vest4		0.23
MPC		0.40
ClinPred		0.016	T
GERP RS		5.7
Varity_R		0.12
gMVP		0.17
Mutation Taster		=97/3	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: rs415895; hg19: chr11-9769562; COSMIC: COSV59664349;