chr2-54457420-A-G

Variant names:

• chr2-54457420-A-G
• rs11898505
• NM_003128.3:c.-48+902A>G

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+902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,478 control chromosomes in the GnomAD database, including 45,046 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 0.76 (44952 hom., cov: 31)
  • Exomes 𝑓: 0.63 (94 hom.)
• Consequence: SPTBN1 NM_003128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• Publications: 45 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

ENSG00000304706 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.-48+902A>G		intron	N/A	NP_003119.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.-48+902A>G		intron	N/A	ENSP00000349259.4
	SPTBN1	ENST00000389980.7	TSL:1	c.-48+113A>G		intron	N/A	ENSP00000374630.3
	ENSG00000304706	ENST00000805725.1		n.188+332T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115247 AN: 151904 Hom.: 44895 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.625 AC: 285 AN: 456 Hom.: 94 AF XY: 0.592 AC XY: 167 AN XY: 282

African (AFR) AF: 1.00 AC: 14 AN: 14

American (AMR) AF: 0.875 AC: 7 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 7 AN: 8

East Asian (EAS) AF: 0.800 AC: 24 AN: 30

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.700 AC: 21 AN: 30

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.568 AC: 193 AN: 340

Other (OTH) AF: 0.750 AC: 18 AN: 24

GnomAD4 genome AF: 0.759 AC: 115362 AN: 152022 Hom.: 44952 Cov.: 31 AF XY: 0.767 AC XY: 56966 AN XY: 74294

African (AFR) AF: 0.934 AC: 38788 AN: 41526

American (AMR) AF: 0.755 AC: 11546 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2260 AN: 3470

East Asian (EAS) AF: 0.875 AC: 4498 AN: 5142

South Asian (SAS) AF: 0.800 AC: 3853 AN: 4814

European-Finnish (FIN) AF: 0.763 AC: 8062 AN: 10560

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 43982 AN: 67908

Other (OTH) AF: 0.719 AC: 1515 AN: 2108

Alfa AF: 0.681 Hom.: 140004

Bravo AF: 0.765

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.54
PhyloP100		-0.85
PromoterAI		-0.0066	Neutral
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: rs11898505; hg19: chr2-54684557;