1-158611097-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003126.4(SPTA1):c.*167A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 913,686 control chromosomes in the GnomAD database, including 31,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5056 hom., cov: 29)

Exomes 𝑓: 0.26 ( 26465 hom. )

Consequence

SPTA1
NM_003126.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.874

Variant links:

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 links:

OR10Z1 (HGNC:14996): (olfactory receptor family 10 subfamily Z member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR10Z1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-158611097-T-C is Benign according to our data. Variant chr1-158611097-T-C is described in ClinVar as [Benign]. Clinvar id is 292923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-158611097-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPTA1	NM_003126.4 link	c.*167A>G		3_prime_UTR_variant	Exon 52 of 52	ENST00000643759.2	NP_003117.2	P02549-1
OR10Z1	NM_001004478.2 link	c.*3717T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000641002.1	NP_001004478.1	Q8NGY1A0A126GV63

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPTA1	ENST00000643759 link	c.*167A>G	3_prime_UTR_variant	Exon 52 of 52		NM_003126.4	ENSP00000495214.1	P02549-1
OR10Z1	ENST00000641002.1 link	c.*3717T>C	3_prime_UTR_variant	Exon 2 of 2		NM_001004478.2	ENSP00000493003.1	Q8NGY1
SPTA1	ENST00000485680.1 link	n.*111A>G	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38208

AN:

150226

Hom.:

5052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.257

AC:

196253

AN:

763342

Hom.:

26465

Cov.:

AF XY:

0.257

AC XY:

100466

AN XY:

390480

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.270

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.254

AC:

38241

AN:

150344

Hom.:

5056

Cov.:

AF XY:

0.256

AC XY:

18762

AN XY:

73294

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.182

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.288

Gnomad4 OTH

AF:

0.263

Alfa

AF:

0.269

Hom.:

1475

Bravo

AF:

0.244

Asia WGS

AF:

0.214

AC:

747

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Elliptocytosis 2

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary spherocytosis type 3

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pyropoikilocytosis, hereditary

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.7

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over