rs2270052

Positions:

• chr7-2251764-G-A
• chr7-2251764-G-C

Variant summary

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

The variant allele was found at a frequency of 0.296 in 152,778 control chromosomes in the GnomAD database, including 7,992 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 0.30 (7951 hom., cov: 33)
  • Exomes 𝑓: 0.33 (41 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

(HGNC:):

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX8	NM_013321.4	c.*3292C>T		downstream_gene_variant		ENST00000222990.8	NP_037453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8	c.*3292C>T		downstream_gene_variant		1	NM_013321.4	ENSP00000222990.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44934 AN: 152058 Hom.: 7945 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.331 AC: 199 AN: 602 Hom.: 41 Cov.: 0 AF XY: 0.328 AC XY: 103 AN XY: 314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.295 AC: 44961 AN: 152176 Hom.: 7951 Cov.: 33 AF XY: 0.299 AC XY: 22201 AN XY: 74366

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.314

Alfa AF: 0.302 Hom.: 1664

Bravo AF: 0.293

Asia WGS AF: 0.447 AC: 1552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.013
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2270052; hg19: chr7-2291399;