rs4923918

chr15-41868745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016642.4(SPTBN5):c.5854-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 709,444 control chromosomes in the GnomAD database, including 1,359 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 0.044 (258 hom., cov: 33)
  • Exomes 𝑓: 0.052 (1101 hom.)
• Consequence: SPTBN5 NM_016642.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.787

Genes affected

SPTBN5 (HGNC:15680): (spectrin beta, non-erythrocytic 5) Enables several functions, including cytoskeletal protein binding activity; dynein intermediate chain binding activity; and identical protein binding activity. Acts upstream of or within Golgi organization and lysosomal transport. Located in cytoplasm; photoreceptor connecting cilium; and photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTBN5	NM_016642.4	c.5854-144C>T		intron_variant		ENST00000320955.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTBN5	ENST00000320955.8	c.5854-144C>T		intron_variant		1	NM_016642.4	P1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6636 AN: 152120 Hom.: 258 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0591

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0523 AC: 29128 AN: 557206 Hom.: 1101 AF XY: 0.0527 AC XY: 15259 AN XY: 289656

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0814

Gnomad4 ASJ exome AF: 0.0378

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.0239

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0454

GnomAD4 genome AF: 0.0436 AC: 6639 AN: 152238 Hom.: 258 Cov.: 33 AF XY: 0.0439 AC XY: 3264 AN XY: 74430

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0681

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.0201

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0416 Hom.: 24

Bravo AF: 0.0494

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.9
Dann	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4923918; hg19: chr15-42160943; COSMIC: COSV58021465; COSMIC: COSV58021465;