rs1695769

Positions:

• chr14-64748447-G-A

Variant summary

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

The NM_001355436.2(SPTB):​c.*859C>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 0.14 in 152,244 control chromosomes in the GnomAD database, including 1,749 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 0.14 (1749 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: SPTB NM_001355436.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

Genes affected

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]

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]

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 = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHG3	NM_001308147.2	c.*4744G>A		3_prime_UTR_variant	17/17	ENST00000247226.13
SPTB	NM_001355436.2	c.*859C>T		3_prime_UTR_variant	36/36	ENST00000644917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHG3	ENST00000247226.13	c.*4744G>A		3_prime_UTR_variant	17/17	1	NM_001308147.2	A2
SPTB	ENST00000644917.1	c.*859C>T		3_prime_UTR_variant	36/36		NM_001355436.2	P1
PLEKHG3	ENST00000634379.2	c.*4744G>A		3_prime_UTR_variant	17/17	1		P4
SPTB	ENST00000389722.7	c.*859C>T		3_prime_UTR_variant	35/35	2		P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21329 AN: 152052 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.135 AC: 10 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.188 AC XY: 9 AN XY: 48

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.140 AC: 21346 AN: 152170 Hom.: 1749 Cov.: 32 AF XY: 0.138 AC XY: 10292 AN XY: 74388

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.124

Alfa AF: 0.126 Hom.: 922

Bravo AF: 0.142

Asia WGS AF: 0.114 AC: 397 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	0.54
DANN	Benign	0.69

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: rs1695769; hg19: chr14-65215165;