1-158612294-T-C

Variant names:

• chr1-158612294-T-C
• rs1557615
• NM_001004478.2:c.*4914T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004478.2. 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
	OR10Z1	NM_001004478.2	MANE Select	c.*4914T>C		3_prime_UTR	Exon 2 of 2	NP_001004478.1
	SPTA1	NM_003126.4	MANE Select	c.7134+523A>G		intron	N/A	NP_003117.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10Z1	ENST00000641002.1	MANE Select	c.*4914T>C		3_prime_UTR	Exon 2 of 2	ENSP00000493003.1
	SPTA1	ENST00000643759.2	MANE Select	c.7134+523A>G		intron	N/A	ENSP00000495214.1

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

African (AFR) AF: 0.359 AC: 97 AN: 270

American (AMR) AF: 0.518 AC: 1459 AN: 2814

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 204 AN: 392

East Asian (EAS) AF: 0.590 AC: 893 AN: 1514

South Asian (SAS) AF: 0.371 AC: 1262 AN: 3404

European-Finnish (FIN) AF: 0.574 AC: 556 AN: 968

Middle Eastern (MID) AF: 0.411 AC: 23 AN: 56

European-Non Finnish (NFE) AF: 0.522 AC: 8739 AN: 16750

Other (OTH) AF: 0.532 AC: 704 AN: 1324

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

African (AFR) AF: 0.424 AC: 17559 AN: 41444

American (AMR) AF: 0.544 AC: 8311 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3206 AN: 5142

South Asian (SAS) AF: 0.433 AC: 2085 AN: 4816

European-Finnish (FIN) AF: 0.638 AC: 6735 AN: 10556

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37560 AN: 67940

Other (OTH) AF: 0.542 AC: 1145 AN: 2114

Alfa AF: 0.542 Hom.: 16165

Bravo AF: 0.515

Asia WGS AF: 0.558 AC: 1938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.3
DANN	Benign	0.85
PhyloP100		-0.96
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: rs1557615; hg19: chr1-158582084;