2-54624163-G-A

Variant names:

• chr2-54624163-G-A
• rs2971886
• NM_003128.3:c.1182+567G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003128.3(SPTBN1):​c.1182+567G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,954 control chromosomes in the GnomAD database, including 22,946 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 0.55 (22946 hom., cov: 32)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 7 publications found

Genes affected

SPTBN1 (HGNC:11275): (spectrin beta, non-erythrocytic 1) 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 contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SPTBN1 Gene-Disease associations (from GenCC):

• developmental delay, impaired speech, and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003128.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	NM_003128.3	MANE Select	c.1182+567G>A		intron	N/A	NP_003119.2
	SPTBN1	NM_178313.3		c.1143+567G>A		intron	N/A	NP_842565.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.1182+567G>A		intron	N/A	ENSP00000349259.4
	SPTBN1	ENST00000333896.5	TSL:1	c.1143+567G>A		intron	N/A	ENSP00000334156.5
	SPTBN1	ENST00000389980.7	TSL:1	c.1182+567G>A		intron	N/A	ENSP00000374630.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83033 AN: 151834 Hom.: 22910 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.547 AC: 83120 AN: 151954 Hom.: 22946 Cov.: 32 AF XY: 0.552 AC XY: 40998 AN XY: 74262

African (AFR) AF: 0.518 AC: 21427 AN: 41400

American (AMR) AF: 0.609 AC: 9306 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1918 AN: 5158

South Asian (SAS) AF: 0.540 AC: 2596 AN: 4804

European-Finnish (FIN) AF: 0.656 AC: 6933 AN: 10566

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37070 AN: 67958

Other (OTH) AF: 0.563 AC: 1187 AN: 2108

Alfa AF: 0.545 Hom.: 26317

Bravo AF: 0.540

Asia WGS AF: 0.495 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.44
PhyloP100		-0.92
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: rs2971886; hg19: chr2-54851300;