dbSNP rs1695769: SPTB:c.*859C>T (chr14-64748447-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_001355436.2(SPTB):c.*859C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,244 control chromosomes in the GnomAD database, including 1,749 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 0.14 ( 1749 hom., cov: 32)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

SPTB
NM_001355436.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

6 publications found

Variant links:

Genes affected

SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

SPTB links:

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHG3 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 (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTB	NM_001355436.2 link	c.*859C>T		3_prime_UTR_variant	Exon 36 of 36	ENST00000644917.1	NP_001342365.1
PLEKHG3	NM_001308147.2 link	c.*4744G>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000247226.13	NP_001295076.1	A1L390-1A0A2X0SFH4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTB	ENST00000644917.1 link	c.*859C>T	3_prime_UTR_variant	Exon 36 of 36		NM_001355436.2	ENSP00000495909.1	P11277-2
PLEKHG3	ENST00000247226.13 link	c.*4744G>A	3_prime_UTR_variant	Exon 17 of 17	1	NM_001308147.2	ENSP00000247226.8	A1L390-1
PLEKHG3	ENST00000634379.2 link	c.*4744G>A	3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000489373.2	A0A0U1RR71
SPTB	ENST00000389722.7 link	c.*859C>T	3_prime_UTR_variant	Exon 35 of 35	2		ENSP00000374372.3	P11277-2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21329

AN:

152052

Hom.:

1751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.0971

Gnomad EAS

AF:

0.0118

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0916

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.124

GnomAD4 exome

AF:

0.135

AC:

AN:

Hom.:

Cov.:

AF XY:

0.188

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.140

AC:

21346

AN:

152170

Hom.:

1749

Cov.:

AF XY:

0.138

AC XY:

10292

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.223

AC:

9256

AN:

41466

American (AMR)

AF:

0.102

AC:

1563

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0971

AC:

337

AN:

3470

East Asian (EAS)

AF:

0.0116

AC:

AN:

5178

South Asian (SAS)

AF:

0.135

AC:

652

AN:

4826

European-Finnish (FIN)

AF:

0.0916

AC:

972

AN:

10614

Middle Eastern (MID)

AF:

0.0753

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.120

AC:

8132

AN:

67986

Other (OTH)

AF:

0.124

AC:

263

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

934

1867

2801

3734

4668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.127

Hom.:

1140

Bravo

AF:

0.142

Asia WGS

AF:

0.114

AC:

397

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.54

(source)

DANN

Benign

0.69

PhyloP100

-1.9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over