rs4902311

Variant names:

• chr14-64775215-G-A
• rs4902311
• NM_001355436.2:c.4752C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-64775215-G-A
• chr14-64775215-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001355436.2(SPTB):​c.4752C>T​(p.Asn1584Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 1,613,800 control chromosomes in the GnomAD database, including 4,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (296 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4302 hom.)
• Consequence: SPTB NM_001355436.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.672
• Publications: 14 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 14-64775215-G-A is Benign according to our data. Variant chr14-64775215-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.672 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 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.4752C>T	p.Asn1584Asn	synonymous	Exon 23 of 36	NP_001342365.1
	SPTB	NM_001024858.4		c.4752C>T	p.Asn1584Asn	synonymous	Exon 22 of 35	NP_001020029.1
	SPTB	NM_001355437.2		c.4752C>T	p.Asn1584Asn	synonymous	Exon 23 of 32	NP_001342366.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	ENST00000644917.1	MANE Select	c.4752C>T	p.Asn1584Asn	synonymous	Exon 23 of 36	ENSP00000495909.1
	SPTB	ENST00000553938.5	TSL:1	c.747C>T	p.Asn249Asn	synonymous	Exon 4 of 18	ENSP00000451324.1
	SPTB	ENST00000389722.7	TSL:2	c.4752C>T	p.Asn1584Asn	synonymous	Exon 22 of 35	ENSP00000374372.3

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8725 AN: 152184 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0772

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0603 AC: 15135 AN: 251122 AF XY: 0.0607

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.0505

Gnomad EAS exome AF: 0.0253

Gnomad FIN exome AF: 0.0763

Gnomad NFE exome AF: 0.0842

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0730 AC: 106737 AN: 1461498 Hom.: 4302 Cov.: 33 AF XY: 0.0722 AC XY: 52475 AN XY: 727074

African (AFR) AF: 0.0147 AC: 493 AN: 33480

American (AMR) AF: 0.0436 AC: 1949 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 1355 AN: 26134

East Asian (EAS) AF: 0.0161 AC: 640 AN: 39700

South Asian (SAS) AF: 0.0303 AC: 2614 AN: 86258

European-Finnish (FIN) AF: 0.0788 AC: 4178 AN: 53050

Middle Eastern (MID) AF: 0.0383 AC: 221 AN: 5768

European-Non Finnish (NFE) AF: 0.0821 AC: 91302 AN: 1111990

Other (OTH) AF: 0.0660 AC: 3985 AN: 60394

GnomAD4 genome AF: 0.0573 AC: 8730 AN: 152302 Hom.: 296 Cov.: 32 AF XY: 0.0572 AC XY: 4263 AN XY: 74464

African (AFR) AF: 0.0182 AC: 755 AN: 41578

American (AMR) AF: 0.0529 AC: 810 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5182

South Asian (SAS) AF: 0.0288 AC: 139 AN: 4824

European-Finnish (FIN) AF: 0.0772 AC: 819 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5766 AN: 68012

Other (OTH) AF: 0.0440 AC: 93 AN: 2116

Alfa AF: 0.0716 Hom.: 997

Bravo AF: 0.0531

Asia WGS AF: 0.0570 AC: 200 AN: 3478

EpiCase AF: 0.0759

EpiControl AF: 0.0762

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Elliptocytosis (1)
-	-	1	not specified (1)
-	-	1	Spherocytosis, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.7
DANN	Benign	0.83
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs4902311; hg19: chr14-65241933; COSMIC: COSV67636304;