19-40487509-C-T

Variant names:

• chr19-40487509-C-T
• rs117119201
• NM_020971.3:c.170-188C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.231

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]

ACMG classification

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
SPTBN4	NM_020971.3	c.170-188C>T		intron_variant	Intron 2 of 35	ENST00000598249.6	NP_066022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPTBN4	ENST00000598249.6	c.170-188C>T		intron_variant	Intron 2 of 35	1	NM_020971.3	ENSP00000469242.1
SPTBN4	ENST00000352632.7	c.170-188C>T		intron_variant	Intron 2 of 35	5		ENSP00000263373.2
SPTBN4	ENST00000595535.5	c.170-188C>T		intron_variant	Intron 2 of 26	5		ENSP00000470693.1

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 11997 AN: 149966 Hom.: 525 Cov.: 31

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

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

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

Other links and lift over

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