chr14-64852643-G-A

Variant names:

• chr14-64852643-G-A
• rs35955841
• NM_001355436.2:c.-52+27149C>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.-52+27149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,994 control chromosomes in the GnomAD database, including 18,076 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 0.44 (18076 hom., cov: 31)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.654
• Publications: 5 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]

SPTB Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• elliptocytosis 3

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary elliptocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary spherocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 (NFE) allele frequency at 95% confidence interval = 0.592 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.-52+27149C>T		intron	N/A	NP_001342365.1
	SPTB	NM_001355437.2		c.-52+27149C>T		intron	N/A	NP_001342366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	ENST00000644917.1	MANE Select	c.-52+27149C>T		intron	N/A	ENSP00000495909.1
	SPTB	ENST00000389720.4	TSL:5	c.-52+27149C>T		intron	N/A	ENSP00000374370.4

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66257 AN: 151876 Hom.: 18074 Cov.: 31

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66261 AN: 151994 Hom.: 18076 Cov.: 31 AF XY: 0.435 AC XY: 32305 AN XY: 74272

African (AFR) AF: 0.111 AC: 4605 AN: 41474

American (AMR) AF: 0.557 AC: 8506 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1784 AN: 3466

East Asian (EAS) AF: 0.192 AC: 990 AN: 5166

South Asian (SAS) AF: 0.448 AC: 2159 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6054 AN: 10538

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40580 AN: 67936

Other (OTH) AF: 0.449 AC: 948 AN: 2112

Alfa AF: 0.513 Hom.: 8109

Bravo AF: 0.415

Asia WGS AF: 0.315 AC: 1094 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	7.9
DANN	Benign	0.74
PhyloP100		0.65
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: rs35955841; hg19: chr14-65319361;