rs11622977

Variant names:

• chr14-64767290-G-A
• rs11622977
• NM_001355436.2:c.6269+13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001355436.2(SPTB):​c.6269+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,462 control chromosomes in the GnomAD database, including 12,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2927 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10065 hom.)
• Consequence: SPTB NM_001355436.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.62
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• elliptocytosis 3

  Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-64767290-G-A is Benign according to our data. Variant chr14-64767290-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	NM_001355436.2	MANE Select	c.6269+13C>T		intron	N/A	NP_001342365.1	P11277-2
	SPTB	NM_001024858.4		c.6269+13C>T		intron	N/A	NP_001020029.1	P11277-2
	SPTB	NM_001355437.2		c.6269+13C>T		intron	N/A	NP_001342366.1	P11277-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTB	ENST00000644917.1	MANE Select	c.6269+13C>T		intron	N/A	ENSP00000495909.1	P11277-2
	SPTB	ENST00000553938.5	TSL:1	c.2264+13C>T		intron	N/A	ENSP00000451324.1	H0YJE6
	SPTB	ENST00000389722.7	TSL:2	c.6269+13C>T		intron	N/A	ENSP00000374372.3	P11277-2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25018 AN: 152034 Hom.: 2921 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.139

GnomAD2 exomes AF: 0.104 AC: 26102 AN: 251210 AF XY: 0.0997

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.0929

Gnomad EAS exome AF: 0.00913

Gnomad FIN exome AF: 0.0825

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0999

GnomAD4 exome AF: 0.108 AC: 157941 AN: 1461310 Hom.: 10065 Cov.: 33 AF XY: 0.106 AC XY: 77279 AN XY: 727006

African (AFR) AF: 0.342 AC: 11447 AN: 33470

American (AMR) AF: 0.0698 AC: 3122 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 2575 AN: 26132

East Asian (EAS) AF: 0.00557 AC: 221 AN: 39700

South Asian (SAS) AF: 0.0687 AC: 5922 AN: 86252

European-Finnish (FIN) AF: 0.0854 AC: 4532 AN: 53060

Middle Eastern (MID) AF: 0.0902 AC: 520 AN: 5768

European-Non Finnish (NFE) AF: 0.111 AC: 122918 AN: 1111826

Other (OTH) AF: 0.111 AC: 6684 AN: 60382

GnomAD4 genome AF: 0.165 AC: 25053 AN: 152152 Hom.: 2927 Cov.: 33 AF XY: 0.160 AC XY: 11924 AN XY: 74396

African (AFR) AF: 0.335 AC: 13907 AN: 41492

American (AMR) AF: 0.0998 AC: 1525 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.00675 AC: 35 AN: 5188

South Asian (SAS) AF: 0.0637 AC: 307 AN: 4820

European-Finnish (FIN) AF: 0.0787 AC: 835 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7674 AN: 67980

Other (OTH) AF: 0.138 AC: 291 AN: 2106

Alfa AF: 0.120 Hom.: 1178

Bravo AF: 0.172

Asia WGS AF: 0.0680 AC: 239 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Elliptocytosis (1)
-	-	1	Spherocytosis, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.32
PhyloP100		-1.6
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: rs11622977; hg19: chr14-65234008;