2-54662253-C-T

Variant names:

• chr2-54662253-C-T
• rs1047499
• ENST00000333896.5:c.*2167C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_178313.3(SPTBN1):​c.*2167C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 985,206 control chromosomes in the GnomAD database, including 270,713 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 0.79 (48655 hom., cov: 32)
  • Exomes 𝑓: 0.73 (222058 hom.)
• Consequence: SPTBN1 NM_178313.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 8 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-AS2 (HGNC:40563): (SPTBN1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• 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_178313.3. 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.6421-2200C>T		intron	N/A	NP_003119.2
	SPTBN1	NM_178313.3		c.*2167C>T		3_prime_UTR	Exon 31 of 31	NP_842565.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTBN1	ENST00000333896.5	TSL:1	c.*2167C>T		3_prime_UTR	Exon 31 of 31	ENSP00000334156.5
	SPTBN1	ENST00000356805.9	TSL:1 MANE Select	c.6421-2200C>T		intron	N/A	ENSP00000349259.4
	SPTBN1	ENST00000898760.1		c.6421-2200C>T		intron	N/A	ENSP00000568819.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120685 AN: 152058 Hom.: 48593 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.729 AC: 607462 AN: 833030 Hom.: 222058 Cov.: 39 AF XY: 0.730 AC XY: 280635 AN XY: 384686

African (AFR) AF: 0.955 AC: 15083 AN: 15786

American (AMR) AF: 0.739 AC: 727 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 3722 AN: 5150

East Asian (EAS) AF: 0.585 AC: 2124 AN: 3630

South Asian (SAS) AF: 0.707 AC: 11644 AN: 16458

European-Finnish (FIN) AF: 0.771 AC: 225 AN: 292

Middle Eastern (MID) AF: 0.719 AC: 1164 AN: 1620

European-Non Finnish (NFE) AF: 0.726 AC: 552871 AN: 761810

Other (OTH) AF: 0.729 AC: 19902 AN: 27300

GnomAD4 genome AF: 0.794 AC: 120807 AN: 152176 Hom.: 48655 Cov.: 32 AF XY: 0.792 AC XY: 58932 AN XY: 74392

African (AFR) AF: 0.933 AC: 38782 AN: 41552

American (AMR) AF: 0.765 AC: 11682 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2494 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2955 AN: 5166

South Asian (SAS) AF: 0.706 AC: 3405 AN: 4826

European-Finnish (FIN) AF: 0.791 AC: 8365 AN: 10572

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50528 AN: 67992

Other (OTH) AF: 0.783 AC: 1653 AN: 2112

Alfa AF: 0.755 Hom.: 43284

Bravo AF: 0.796

Asia WGS AF: 0.680 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.51
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: rs1047499; hg19: chr2-54889390;