1-158612294-T-C

Position:

• chr1-158612294-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004478.2(OR10Z1):​c.*4914T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 179,452 control chromosomes in the GnomAD database, including 24,869 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21074 hom., cov: 32)
  • Exomes 𝑓: 0.51 (3795 hom.)
• Consequence: OR10Z1 NM_001004478.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

Genes affected

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10Z1	NM_001004478.2	c.*4914T>C		3_prime_UTR_variant	2/2	ENST00000641002.1	NP_001004478.1
SPTA1	NM_003126.4	c.7134+523A>G		intron_variant		ENST00000643759.2	NP_003117.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10Z1	ENST00000641002.1	c.*4914T>C		3_prime_UTR_variant	2/2		NM_001004478.2	ENSP00000493003	P1
SPTA1	ENST00000643759.2	c.7134+523A>G		intron_variant			NM_003126.4	ENSP00000495214	P1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79183 AN: 151842 Hom.: 21048 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.507 AC: 13937 AN: 27492 Hom.: 3795 Cov.: 0 AF XY: 0.503 AC XY: 7231 AN XY: 14374

Gnomad4 AFR exome AF: 0.359

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.590

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.522 AC: 79258 AN: 151960 Hom.: 21074 Cov.: 32 AF XY: 0.527 AC XY: 39163 AN XY: 74262

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.542

Alfa AF: 0.546 Hom.: 12956

Bravo AF: 0.515

Asia WGS AF: 0.558 AC: 1938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.3
DANN	Benign	0.85

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: rs1557615; hg19: chr1-158582084;