rs857721

Positions:

• chr1-158642758-T-A
• chr1-158642758-T-C
• chr1-158642758-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003126.4(SPTA1):​c.4605+56A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,612,634 control chromosomes in the GnomAD database, including 58,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4728 hom., cov: 31)
  • Exomes 𝑓: 0.27 (54229 hom.)
• Consequence: SPTA1 NM_003126.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-158642758-T-A is Benign according to our data. Variant chr1-158642758-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPTA1	NM_003126.4	c.4605+56A>T		intron_variant		ENST00000643759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPTA1	ENST00000643759.2	c.4605+56A>T		intron_variant			NM_003126.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35147 AN: 151944 Hom.: 4721 Cov.: 31

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.267 AC: 390174 AN: 1460572 Hom.: 54229 Cov.: 32 AF XY: 0.264 AC XY: 191818 AN XY: 726634

Gnomad4 AFR exome AF: 0.0893

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.231 AC: 35175 AN: 152062 Hom.: 4728 Cov.: 31 AF XY: 0.236 AC XY: 17529 AN XY: 74336

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.255

Alfa AF: 0.246 Hom.: 2749

Bravo AF: 0.230

Asia WGS AF: 0.342 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs857721; hg19: chr1-158612548; COSMIC: COSV63750573; COSMIC: COSV63750573;