Genetic Variant SELL:p.Phe193Leu (chr1-169707345-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000655.5(SELL):c.577T>C(p.Phe193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,607,898 control chromosomes in the GnomAD database, including 51,524 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F193Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.21 ( 3854 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47670 hom. )

Consequence

SELL
NM_000655.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

38 publications found

Variant links:

Genes affected

SELL (HGNC:10720): (selectin L) This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

SELL links:

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

FIRRM links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014271736).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5 link	c.577T>C	p.Phe193Leu	missense_variant	Exon 4 of 9	ENST00000236147.6	NP_000646.3	P14151-1
SELL	NR_029467.2 link	n.546T>C		non_coding_transcript_exon_variant	Exon 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELL	ENST00000236147.6 link	c.577T>C	p.Phe193Leu	missense_variant	Exon 4 of 9	1	NM_000655.5	ENSP00000236147.5		P14151-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32356

AN:

151898

Hom.:

3855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.00502

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.227

GnomAD2 exomes

AF:

0.206

AC:

50921

AN:

247268

AF XY:

0.211

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.00549

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.249

AC:

361860

AN:

1455882

Hom.:

47670

Cov.:

AF XY:

0.247

AC XY:

179173

AN XY:

724332

show subpopulations

African (AFR)

AF:

0.150

AC:

4980

AN:

33308

American (AMR)

AF:

0.136

AC:

6054

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

6993

AN:

25992

East Asian (EAS)

AF:

0.00404

AC:

160

AN:

39590

South Asian (SAS)

AF:

0.164

AC:

14148

AN:

86032

European-Finnish (FIN)

AF:

0.209

AC:

11167

AN:

53308

Middle Eastern (MID)

AF:

0.283

AC:

1621

AN:

5732

European-Non Finnish (NFE)

AF:

0.273

AC:

302840

AN:

1107412

Other (OTH)

AF:

0.231

AC:

13897

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11371

22742

34113

45484

56855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.213

AC:

32343

AN:

152016

Hom.:

3854

Cov.:

AF XY:

0.207

AC XY:

15406

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.158

AC:

6537

AN:

41478

American (AMR)

AF:

0.188

AC:

2865

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

885

AN:

3468

East Asian (EAS)

AF:

0.00522

AC:

AN:

5168

South Asian (SAS)

AF:

0.149

AC:

719

AN:

4828

European-Finnish (FIN)

AF:

0.209

AC:

2211

AN:

10566

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18355

AN:

67954

Other (OTH)

AF:

0.225

AC:

475

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1267

2534

3801

5068

6335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.247

Hom.:

12181

Bravo

AF:

0.210

TwinsUK

AF:

0.275

AC:

1021

ALSPAC

AF:

0.265

AC:

1021

ESP6500AA

AF:

0.143

AC:

541

ESP6500EA

AF:

0.267

AC:

2204

ExAC

AF:

0.207

AC:

25050

Asia WGS

AF:

0.0600

AC:

207

AN:

3478

EpiCase

AF:

0.280

EpiControl

AF:

0.285

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.64

PhyloP100

0.23

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.29

Sift

Benign

0.38

Sift4G

Benign

0.37

Vest4

0.13

MPC

0.021

ClinPred

0.014

GERP RS

3.2

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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1-169707345-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over