rs7140

Positions:

• chr16-28984436-C-A
• chr16-28984436-C-G

Variant summary

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

The NM_032038.3(SPNS1):​c.*137C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 854,248 control chromosomes in the GnomAD database, including 229,198 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 0.77 (45475 hom., cov: 34)
  • Exomes 𝑓: 0.72 (183723 hom.)
• Consequence: SPNS1 NM_032038.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

SPNS1 (HGNC:30621): (SPNS lysolipid transporter 1, lysophospholipid) Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261067 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.219226E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPNS1	NM_032038.3	c.*137C>A		3_prime_UTR_variant	12/12	ENST00000311008.16	NP_114427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPNS1	ENST00000311008.16	c.*137C>A		3_prime_UTR_variant	12/12	1	NM_032038.3	ENSP00000309945.11

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116330 AN: 152056 Hom.: 45424 Cov.: 34

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.779

GnomAD3 exomes AF: 0.729 AC: 101296 AN: 138880 Hom.: 37943 AF XY: 0.739 AC XY: 55820 AN XY: 75520

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.927

Gnomad SAS exome AF: 0.809

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.717 AC: 503712 AN: 702074 Hom.: 183723 Cov.: 9 AF XY: 0.722 AC XY: 267345 AN XY: 370072

Gnomad4 AFR exome AF: 0.920

Gnomad4 AMR exome AF: 0.559

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.807

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.765 AC: 116427 AN: 152174 Hom.: 45475 Cov.: 34 AF XY: 0.764 AC XY: 56851 AN XY: 74390

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.780

Alfa AF: 0.721 Hom.: 54377

Bravo AF: 0.771

TwinsUK AF: 0.698 AC: 2587

ALSPAC AF: 0.691 AC: 2665

ExAC AF: 0.644 AC: 44792

Asia WGS AF: 0.825 AC: 2872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.5
DANN	Benign	0.90
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	7.2e-7	T
PROVEAN	Benign	-0.17	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
GERP RS		0.77
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: rs7140; hg19: chr16-28995757;