dbSNP rs4923918: SPTBN5:c.5854-144C>T (chr15-41868745-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016642.4(SPTBN5):c.5854-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 709,444 control chromosomes in the GnomAD database, including 1,359 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 0.044 ( 258 hom., cov: 33)

Exomes 𝑓: 0.052 ( 1101 hom. )

Consequence

SPTBN5
NM_016642.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.787

Publications

3 publications found

Variant links:

Genes affected

SPTBN5 (HGNC:15680): (spectrin beta, non-erythrocytic 5) Enables several functions, including cytoskeletal protein binding activity; dynein intermediate chain binding activity; and identical protein binding activity. Acts upstream of or within Golgi organization and lysosomal transport. Located in cytoplasm; photoreceptor connecting cilium; and photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPTBN5 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016642.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN5	NM_016642.4	MANE Select	c.5854-144C>T		intron	N/A	NP_057726.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN5	ENST00000320955.8	TSL:1 MANE Select	c.5854-144C>T		intron	N/A	ENSP00000317790.6

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6636

AN:

152120

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.0591

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0481

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0523

AC:

29128

AN:

557206

Hom.:

1101

AF XY:

0.0527

AC XY:

15259

AN XY:

289656

show subpopulations

African (AFR)

AF:

0.0118

AC:

175

AN:

14840

American (AMR)

AF:

0.0814

AC:

1830

AN:

22490

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

558

AN:

14770

East Asian (EAS)

AF:

0.160

AC:

5054

AN:

31682

South Asian (SAS)

AF:

0.0607

AC:

3106

AN:

51158

European-Finnish (FIN)

AF:

0.0239

AC:

729

AN:

30558

Middle Eastern (MID)

AF:

0.0541

AC:

138

AN:

2552

European-Non Finnish (NFE)

AF:

0.0450

AC:

16190

AN:

359462

Other (OTH)

AF:

0.0454

AC:

1348

AN:

29694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1486

2972

4459

5945

7431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.0436

AC:

6639

AN:

152238

Hom.:

258

Cov.:

AF XY:

0.0439

AC XY:

3264

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0129

AC:

535

AN:

41556

American (AMR)

AF:

0.0681

AC:

1042

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

131

AN:

3470

East Asian (EAS)

AF:

0.180

AC:

926

AN:

5152

South Asian (SAS)

AF:

0.0593

AC:

286

AN:

4822

European-Finnish (FIN)

AF:

0.0201

AC:

213

AN:

10620

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0480

AC:

3265

AN:

67996

Other (OTH)

AF:

0.0577

AC:

122

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

322

643

965

1286

1608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0406

Hom.:

Bravo

AF:

0.0494

Asia WGS

AF:

0.0920

AC:

322

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.9

(source)

DANN

Benign

0.70

PhyloP100

0.79

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over