2-54491044-T-C

Variant names:

• chr2-54491044-T-C
• rs4557020
• NM_003128.3:c.-48+34526T>C

Variant summary

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

The NM_003128.3(SPTBN1):​c.-48+34526T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,946 control chromosomes in the GnomAD database, including 28,846 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 0.60 (28846 hom., cov: 31)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 16 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

C9orf85P1 (HGNC:56317):

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 (AFR) allele frequency at 95% confidence interval = 0.789 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	NM_003128.3	MANE Select	c.-48+34526T>C		intron	N/A	NP_003119.2	Q01082-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.-48+34526T>C		intron	N/A	ENSP00000349259.4	Q01082-1
	SPTBN1	ENST00000389980.7	TSL:1	c.-48+33737T>C		intron	N/A	ENSP00000374630.3	F8W6C1
	SPTBN1	ENST00000898760.1		c.-48+34124T>C		intron	N/A	ENSP00000568819.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91343 AN: 151826 Hom.: 28790 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.602 AC: 91460 AN: 151946 Hom.: 28846 Cov.: 31 AF XY: 0.603 AC XY: 44810 AN XY: 74256

African (AFR) AF: 0.796 AC: 32995 AN: 41442

American (AMR) AF: 0.587 AC: 8957 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3466

East Asian (EAS) AF: 0.616 AC: 3182 AN: 5162

South Asian (SAS) AF: 0.566 AC: 2727 AN: 4814

European-Finnish (FIN) AF: 0.624 AC: 6580 AN: 10538

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.499 AC: 33877 AN: 67954

Other (OTH) AF: 0.540 AC: 1140 AN: 2110

Alfa AF: 0.532 Hom.: 46742

Bravo AF: 0.610

Asia WGS AF: 0.628 AC: 2182 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	1.1
DANN	Benign	0.71
PhyloP100		-0.97
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: rs4557020; hg19: chr2-54718181;