Genetic Variant SDK1:c.1817+131C>T (chr7-3971699-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152744.4(SDK1):c.1817+131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 701,110 control chromosomes in the GnomAD database, including 46,581 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 0.42 ( 15355 hom., cov: 32)

Exomes 𝑓: 0.33 ( 31226 hom. )

Consequence

SDK1
NM_152744.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

Publications

3 publications found

Variant links:

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

SDK1 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 (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4 link	c.1817+131C>T		intron_variant	Intron 12 of 44	ENST00000404826.7	NP_689957.3	Q7Z5N4-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDK1	ENST00000404826.7 link	c.1817+131C>T	intron_variant	Intron 12 of 44	1	NM_152744.4	ENSP00000385899.2	Q7Z5N4-1
SDK1	ENST00000389531.7 link	c.1817+131C>T	intron_variant	Intron 12 of 43	5		ENSP00000374182.3	F8W6X9
SDK1	ENST00000484011.1 link	n.103+131C>T	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63527

AN:

151994

Hom.:

15317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.397

GnomAD4 exome

AF:

0.326

AC:

178968

AN:

548998

Hom.:

31226

AF XY:

0.325

AC XY:

93947

AN XY:

289294

show subpopulations

African (AFR)

AF:

0.674

AC:

10503

AN:

15576

American (AMR)

AF:

0.411

AC:

13288

AN:

32334

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

6634

AN:

17992

East Asian (EAS)

AF:

0.167

AC:

5286

AN:

31580

South Asian (SAS)

AF:

0.327

AC:

18413

AN:

56250

European-Finnish (FIN)

AF:

0.321

AC:

11373

AN:

35412

Middle Eastern (MID)

AF:

0.370

AC:

1047

AN:

2826

European-Non Finnish (NFE)

AF:

0.313

AC:

102299

AN:

327118

Other (OTH)

AF:

0.339

AC:

10125

AN:

29910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5891

11781

17672

23562

29453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1064

2128

3192

4256

5320

<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:

0.418

AC:

63620

AN:

152112

Hom.:

15355

Cov.:

AF XY:

0.415

AC XY:

30867

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.674

AC:

27981

AN:

41492

American (AMR)

AF:

0.388

AC:

5940

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1313

AN:

3468

East Asian (EAS)

AF:

0.174

AC:

898

AN:

5168

South Asian (SAS)

AF:

0.317

AC:

1528

AN:

4822

European-Finnish (FIN)

AF:

0.334

AC:

3533

AN:

10576

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21260

AN:

67980

Other (OTH)

AF:

0.398

AC:

839

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1712

3424

5137

6849

8561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.375

Hom.:

4686

Bravo

AF:

0.434

Asia WGS

AF:

0.264

AC:

921

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.44

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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