19-40472962-C-A

Variant names:

• chr19-40472962-C-A
• rs4306639
• NM_020971.3:c.169+172C>A

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.169+172C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,164 control chromosomes in the GnomAD database, including 3,034 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3034 hom., cov: 32)
• Consequence: SPTBN4 NM_020971.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.395

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=-0.93).
• BP6: Variant 19-40472962-C-A is Benign according to our data. Variant chr19-40472962-C-A is described in ClinVar as [Benign]. Clinvar id is 1262681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTBN4	NM_020971.3	c.169+172C>A		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.169+172C>A		intron_variant	Intron 2 of 35	1	NM_020971.3	ENSP00000469242.1
SPTBN4	ENST00000352632.7	c.169+172C>A		intron_variant	Intron 2 of 35	5		ENSP00000263373.2
SPTBN4	ENST00000595535.5	c.169+172C>A		intron_variant	Intron 2 of 26	5		ENSP00000470693.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27987 AN: 152046 Hom.: 3026 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.184 AC: 28030 AN: 152164 Hom.: 3034 Cov.: 32 AF XY: 0.180 AC XY: 13363 AN XY: 74402

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00597

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.200

Alfa AF: 0.156 Hom.: 2621

Bravo AF: 0.189

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.27

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: rs4306639; hg19: chr19-40978869;