rs4803342

Positions:

• chr19-40476468-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020971.3(SPTBN4):​c.169+3678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,958 control chromosomes in the GnomAD database, including 10,973 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 0.37 (10973 hom., cov: 31)
• Consequence: SPTBN4 NM_020971.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTBN4	NM_020971.3	c.169+3678A>G		intron_variant		ENST00000598249.6	NP_066022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTBN4	ENST00000598249.6	c.169+3678A>G		intron_variant		1	NM_020971.3	ENSP00000469242.1
SPTBN4	ENST00000352632.7	c.169+3678A>G		intron_variant		5		ENSP00000263373.2
SPTBN4	ENST00000595535.5	c.169+3678A>G		intron_variant		5		ENSP00000470693.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56225 AN: 151840 Hom.: 10957 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56278 AN: 151958 Hom.: 10973 Cov.: 31 AF XY: 0.359 AC XY: 26666 AN XY: 74236

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.0949

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.388

Alfa AF: 0.380 Hom.: 6590

Bravo AF: 0.375

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.73

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: rs4803342; hg19: chr19-40982375;