19-40487509-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020971.3(SPTBN4):​c.170-188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 150,090 control chromosomes in the GnomAD database, including 527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.080 ( 527 hom., cov: 31)

Consequence

SPTBN4
NM_020971.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.231
Variant links:
Genes affected
SPTBN4 (HGNC:14896): (spectrin beta, non-erythrocytic 4) Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein localizes to the nuclear matrix, PML nuclear bodies, and cytoplasmic vesicles. A highly similar gene in the mouse is required for localization of specific membrane proteins in polarized regions of neurons. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 19-40487509-C-T is Benign according to our data. Variant chr19-40487509-C-T is described in ClinVar as [Benign]. Clinvar id is 1278919.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPTBN4NM_020971.3 linkc.170-188C>T intron_variant Intron 2 of 35 ENST00000598249.6 NP_066022.2 Q9H254-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPTBN4ENST00000598249.6 linkc.170-188C>T intron_variant Intron 2 of 35 1 NM_020971.3 ENSP00000469242.1 Q9H254-1
SPTBN4ENST00000352632.7 linkc.170-188C>T intron_variant Intron 2 of 35 5 ENSP00000263373.2 Q9H254-1
SPTBN4ENST00000595535.5 linkc.170-188C>T intron_variant Intron 2 of 26 5 ENSP00000470693.1 M0QZQ3

Frequencies

GnomAD3 genomes
AF:
0.0800
AC:
11997
AN:
149966
Hom.:
525
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.121
Gnomad AMI
AF:
0.134
Gnomad AMR
AF:
0.0528
Gnomad ASJ
AF:
0.101
Gnomad EAS
AF:
0.00139
Gnomad SAS
AF:
0.137
Gnomad FIN
AF:
0.0472
Gnomad MID
AF:
0.0685
Gnomad NFE
AF:
0.0661
Gnomad OTH
AF:
0.0913
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0800
AC:
12013
AN:
150090
Hom.:
527
Cov.:
31
AF XY:
0.0800
AC XY:
5867
AN XY:
73348
show subpopulations
Gnomad4 AFR
AF:
0.121
Gnomad4 AMR
AF:
0.0527
Gnomad4 ASJ
AF:
0.101
Gnomad4 EAS
AF:
0.00139
Gnomad4 SAS
AF:
0.138
Gnomad4 FIN
AF:
0.0472
Gnomad4 NFE
AF:
0.0662
Gnomad4 OTH
AF:
0.0908
Alfa
AF:
0.0328
Hom.:
11
Bravo
AF:
0.0777
Asia WGS
AF:
0.0620
AC:
216
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 16, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
3.4
DANN
Benign
0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117119201; hg19: chr19-40993416; COSMIC: COSV58951220; API