chr1-158611097-T-C

Variant names:

• chr1-158611097-T-C
• rs3768535
• NM_003126.4:c.*167A>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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.874
• Publications: 5 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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 292923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	NM_003126.4	MANE Select	c.*167A>G		3_prime_UTR	Exon 52 of 52	NP_003117.2	P02549-1
	OR10Z1	NM_001004478.2	MANE Select	c.*3717T>C		3_prime_UTR	Exon 2 of 2	NP_001004478.1	A0A126GV63

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPTA1	ENST00000643759.2	MANE Select	c.*167A>G		3_prime_UTR	Exon 52 of 52	ENSP00000495214.1	P02549-1
	OR10Z1	ENST00000641002.1	MANE Select	c.*3717T>C		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1	Q8NGY1
	SPTA1	ENST00000485680.1	TSL:3	n.*111A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38208 AN: 150226 Hom.: 5052 Cov.: 29

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.: 10 AF XY: 0.257 AC XY: 100466 AN XY: 390480

African (AFR) AF: 0.198 AC: 3754 AN: 18946

American (AMR) AF: 0.176 AC: 5306 AN: 30148

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 5309 AN: 17142

East Asian (EAS) AF: 0.179 AC: 5437 AN: 30400

South Asian (SAS) AF: 0.240 AC: 14068 AN: 58684

European-Finnish (FIN) AF: 0.270 AC: 8273 AN: 30598

Middle Eastern (MID) AF: 0.230 AC: 622 AN: 2706

European-Non Finnish (NFE) AF: 0.268 AC: 144544 AN: 538972

Other (OTH) AF: 0.250 AC: 8940 AN: 35746

GnomAD4 genome AF: 0.254 AC: 38241 AN: 150344 Hom.: 5056 Cov.: 29 AF XY: 0.256 AC XY: 18762 AN XY: 73294

African (AFR) AF: 0.203 AC: 8295 AN: 40816

American (AMR) AF: 0.221 AC: 3320 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.182 AC: 923 AN: 5068

South Asian (SAS) AF: 0.245 AC: 1162 AN: 4752

European-Finnish (FIN) AF: 0.304 AC: 3109 AN: 10232

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19488 AN: 67732

Other (OTH) AF: 0.263 AC: 544 AN: 2068

Alfa AF: 0.267 Hom.: 1492

Bravo AF: 0.244

Asia WGS AF: 0.214 AC: 747 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Elliptocytosis 2 (1)
-	-	1	Hereditary spherocytosis type 3 (1)
-	-	1	Pyropoikilocytosis, hereditary (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		0.87
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: rs3768535; hg19: chr1-158580887; COSMIC: COSV100779116; COSMIC: COSV100779116;