chr19-40487509-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

SPTBN4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, neuropathy, and deafness

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020971.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN4	NM_020971.3	MANE Select	c.170-188C>T		intron	N/A	NP_066022.2	Q9H254-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN4	ENST00000598249.6	TSL:1 MANE Select	c.170-188C>T		intron	N/A	ENSP00000469242.1	Q9H254-1
	SPTBN4	ENST00000352632.7	TSL:5	c.170-188C>T		intron	N/A	ENSP00000263373.2	Q9H254-1
	SPTBN4	ENST00000595535.5	TSL:5	c.170-188C>T		intron	N/A	ENSP00000470693.1	M0QZQ3

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

African (AFR) AF: 0.121 AC: 4935 AN: 40788

American (AMR) AF: 0.0527 AC: 793 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 346 AN: 3440

East Asian (EAS) AF: 0.00139 AC: 7 AN: 5042

South Asian (SAS) AF: 0.138 AC: 654 AN: 4730

European-Finnish (FIN) AF: 0.0472 AC: 489 AN: 10370

Middle Eastern (MID) AF: 0.0657 AC: 18 AN: 274

European-Non Finnish (NFE) AF: 0.0662 AC: 4461 AN: 67430

Other (OTH) AF: 0.0908 AC: 188 AN: 2070

Alfa AF: 0.0328 Hom.: 11

Bravo AF: 0.0777

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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