rs1288547

Positions:

• chr4-185294982-A-G
• chr4-185294982-A-T

Variant summary

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

The NM_001378034.2(SNX25):​c.1162+6900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,940 control chromosomes in the GnomAD database, including 13,635 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 0.42 (13635 hom., cov: 32)
• Consequence: SNX25 NM_001378034.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

Genes affected

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX25	NM_001378034.2	c.1162+6900A>G		intron_variant		ENST00000652585.2	NP_001364963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX25	ENST00000652585.2	c.1162+6900A>G		intron_variant			NM_001378034.2	ENSP00000498676
SNX25	ENST00000504273.5	c.670+6900A>G		intron_variant		1		ENSP00000426255	P1
SNX25	ENST00000264694.13	c.670+6900A>G		intron_variant		5		ENSP00000264694	P1
SNX25	ENST00000618785.4	c.-18+6900A>G		intron_variant		5		ENSP00000483653

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63975 AN: 151822 Hom.: 13623 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.421 AC: 64030 AN: 151940 Hom.: 13635 Cov.: 32 AF XY: 0.420 AC XY: 31181 AN XY: 74246

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.433

Alfa AF: 0.440 Hom.: 23953

Bravo AF: 0.415

Asia WGS AF: 0.502 AC: 1741 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.62

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: rs1288547; hg19: chr4-186216136;