14-64748447-G-A

Variant names:

• chr14-64748447-G-A
• rs1695769
• NM_001355436.2:c.*859C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355436.2. 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
	SPTB	NM_001355436.2	MANE Select	c.*859C>T		3_prime_UTR	Exon 36 of 36	NP_001342365.1
	PLEKHG3	NM_001308147.2	MANE Select	c.*4744G>A		3_prime_UTR	Exon 17 of 17	NP_001295076.1
	SPTB	NM_001024858.4		c.*859C>T		3_prime_UTR	Exon 35 of 35	NP_001020029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	ENST00000644917.1	MANE Select	c.*859C>T		3_prime_UTR	Exon 36 of 36	ENSP00000495909.1
	PLEKHG3	ENST00000247226.13	TSL:1 MANE Select	c.*4744G>A		3_prime_UTR	Exon 17 of 17	ENSP00000247226.8
	PLEKHG3	ENST00000634379.2	TSL:1	c.*4744G>A		3_prime_UTR	Exon 17 of 17	ENSP00000489373.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

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

European-Non Finnish (NFE) AF: 0.125 AC: 8 AN: 64

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.223 AC: 9256 AN: 41466

American (AMR) AF: 0.102 AC: 1563 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5178

South Asian (SAS) AF: 0.135 AC: 652 AN: 4826

European-Finnish (FIN) AF: 0.0916 AC: 972 AN: 10614

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8132 AN: 67986

Other (OTH) AF: 0.124 AC: 263 AN: 2114

Alfa AF: 0.127 Hom.: 1140

Bravo AF: 0.142

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.69
PhyloP100		-1.9
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: rs1695769; hg19: chr14-65215165;