rs1695770

Positions:

• chr14-64748448-C-T

Variant summary

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

The NM_001355436.2(SPTB):​c.*858G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,144 control chromosomes in the GnomAD database, including 3,878 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 0.21 (3877 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: SPTB NM_001355436.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

Genes affected

SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPTB	NM_001355436.2	c.*858G>A		3_prime_UTR_variant	36/36	ENST00000644917.1	NP_001342365.1
PLEKHG3	NM_001308147.2	c.*4745C>T		3_prime_UTR_variant	17/17	ENST00000247226.13	NP_001295076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPTB	ENST00000644917	c.*858G>A		3_prime_UTR_variant	36/36		NM_001355436.2	ENSP00000495909.1
PLEKHG3	ENST00000247226.13	c.*4745C>T		3_prime_UTR_variant	17/17	1	NM_001308147.2	ENSP00000247226.8
PLEKHG3	ENST00000634379.2	c.*4745C>T		3_prime_UTR_variant	17/17	1		ENSP00000489373.2
SPTB	ENST00000389722	c.*858G>A		3_prime_UTR_variant	35/35	2		ENSP00000374372.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31981 AN: 151964 Hom.: 3873 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0486

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.226 AC: 14 AN: 62 Hom.: 1 Cov.: 0 AF XY: 0.238 AC XY: 10 AN XY: 42

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.185

GnomAD4 genome AF: 0.211 AC: 32015 AN: 152082 Hom.: 3877 Cov.: 32 AF XY: 0.210 AC XY: 15583 AN XY: 74354

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.184

Alfa AF: 0.176 Hom.: 2291

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.59

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: rs1695770; hg19: chr14-65215166;