dbSNP rs4987382: SELL:p.Asn369Asp (chr1-169691798-T-C) – 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.1105A>G(p.Asn369Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00943 in 1,377,586 control chromosomes in the GnomAD database, including 856 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.047 ( 535 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 321 hom. )

Consequence

SELL
NM_000655.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.234

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0012456179).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELL	NM_000655.5 link	c.1105A>G	p.Asn369Asp	missense_variant	Exon 9 of 9	ENST00000236147.6	NP_000646.3
SELL	NR_029467.2 link	n.1074A>G		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SELL	ENST00000236147.6 link	c.1105A>G	p.Asn369Asp	missense_variant	Exon 9 of 9	1	NM_000655.5	ENSP00000236147.5
SELL	ENST00000650983.1 link	c.1144A>G	p.Asn382Asp	missense_variant	Exon 9 of 9			ENSP00000498227.1
SELL	ENST00000497295.1 link	c.97A>G	p.Asn33Asp	missense_variant	Exon 3 of 3	5		ENSP00000498707.1
FIRRM	ENST00000498289.5 link	n.851+7866T>C		intron_variant	Intron 3 of 28	2

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7168

AN:

152172

Hom.:

532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0186

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0126

AC:

1700

AN:

135144

AF XY:

0.00911

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.00731

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000926

Gnomad OTH exome

AF:

0.00680

GnomAD4 exome

AF:

0.00473

AC:

5800

AN:

1225296

Hom.:

321

Cov.:

AF XY:

0.00430

AC XY:

2584

AN XY:

601140

show subpopulations

African (AFR)

AF:

0.155

AC:

3853

AN:

24908

American (AMR)

AF:

0.00849

AC:

163

AN:

19204

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

409

AN:

17744

East Asian (EAS)

AF:

0.0000316

AC:

AN:

31686

South Asian (SAS)

AF:

0.000232

AC:

AN:

47336

European-Finnish (FIN)

AF:

0.0000225

AC:

AN:

44464

Middle Eastern (MID)

AF:

0.00640

AC:

AN:

4846

European-Non Finnish (NFE)

AF:

0.000727

AC:

717

AN:

985926

Other (OTH)

AF:

0.0125

AC:

614

AN:

49182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

203

406

608

811

1014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0472

AC:

7188

AN:

152290

Hom.:

535

Cov.:

AF XY:

0.0460

AC XY:

3422

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.161

AC:

6667

AN:

41522

American (AMR)

AF:

0.0185

AC:

283

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000970

AC:

AN:

68038

Other (OTH)

AF:

0.0388

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

303

607

910

1214

1517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0207

Hom.:

493

Bravo

AF:

0.0530

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.161

AC:

582

ESP6500EA

AF:

0.00246

AC:

ExAC

AF:

0.0148

AC:

1781

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.2

(source)

DANN

Benign

0.87

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.95

PhyloP100

0.23

PrimateAI

Benign

0.33

PROVEAN

Benign

0.72

REVEL

Benign

0.078

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.013

MPC

0.019

ClinPred

0.0028

GERP RS

4.1

Mutation Taster

=100/0

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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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