rs703116

Variant names:

• chr1-158674315-T-A
• rs703116
• NM_003126.4:c.1350+14A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-158674315-T-A
• chr1-158674315-T-C
• chr1-158674315-T-G

Variant summary

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

The NM_003126.4(SPTA1):​c.1350+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,611,594 control chromosomes in the GnomAD database, including 131,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9429 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121661 hom.)
• Consequence: SPTA1 NM_003126.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.806
• Publications: 12 publications found

Genes affected

SPTA1 (HGNC:11272): (spectrin alpha, erythrocytic 1) This gene encodes a member of a family of molecular scaffold proteins that link the plasma membrane to the actin cytoskeleton and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms a component of the erythrocyte plasma membrane. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis-2, pyropoikilocytosis, and spherocytosis, type 3. [provided by RefSeq, Aug 2017]

SPTA1 Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics
• elliptocytosis 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• pyropoikilocytosis, hereditary

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.8).
• BP6: Variant 1-158674315-T-A is Benign according to our data. Variant chr1-158674315-T-A is described in ClinVar as Benign. ClinVar VariationId is 258917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003126.4. 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
	SPTA1	NM_003126.4	MANE Select	c.1350+14A>T		intron	N/A	NP_003117.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	ENST00000643759.2	MANE Select	c.1350+14A>T		intron	N/A	ENSP00000495214.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50229 AN: 151988 Hom.: 9435 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.343

GnomAD2 exomes AF: 0.403 AC: 100403 AN: 249060 AF XY: 0.412

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.355

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.400

GnomAD4 exome AF: 0.404 AC: 589029 AN: 1459488 Hom.: 121661 Cov.: 32 AF XY: 0.409 AC XY: 296681 AN XY: 726244

African (AFR) AF: 0.129 AC: 4319 AN: 33438

American (AMR) AF: 0.416 AC: 18612 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 11020 AN: 26118

East Asian (EAS) AF: 0.454 AC: 17992 AN: 39672

South Asian (SAS) AF: 0.535 AC: 46079 AN: 86202

European-Finnish (FIN) AF: 0.353 AC: 18829 AN: 53368

Middle Eastern (MID) AF: 0.370 AC: 2132 AN: 5760

European-Non Finnish (NFE) AF: 0.402 AC: 446646 AN: 1109906

Other (OTH) AF: 0.388 AC: 23400 AN: 60318

GnomAD4 genome AF: 0.330 AC: 50231 AN: 152106 Hom.: 9429 Cov.: 32 AF XY: 0.333 AC XY: 24724 AN XY: 74338

African (AFR) AF: 0.139 AC: 5758 AN: 41528

American (AMR) AF: 0.389 AC: 5930 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2224 AN: 5174

South Asian (SAS) AF: 0.546 AC: 2629 AN: 4812

European-Finnish (FIN) AF: 0.354 AC: 3753 AN: 10588

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27178 AN: 67962

Other (OTH) AF: 0.342 AC: 722 AN: 2114

Alfa AF: 0.357 Hom.: 1863

Bravo AF: 0.322

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	not specified (3)
-	-	2	Elliptocytosis 2 (2)
-	-	2	Hereditary spherocytosis type 3 (2)
-	-	2	Pyropoikilocytosis, hereditary (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		0.81
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: rs703116; hg19: chr1-158644105; COSMIC: COSV63749143;