rs1288547

Variant names:

• chr4-185294982-A-G
• rs1288547
• NM_001378034.2:c.1162+6900A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378034.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX25	NM_001378034.2	MANE Select	c.1162+6900A>G		intron	N/A	NP_001364963.1	A0A494C0S0
	SNX25	NM_001378032.2		c.1261+6900A>G		intron	N/A	NP_001364961.1
	SNX25	NM_001423234.1		c.1162+6900A>G		intron	N/A	NP_001410163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX25	ENST00000652585.2	MANE Select	c.1162+6900A>G		intron	N/A	ENSP00000498676.1	A0A494C0S0
	SNX25	ENST00000504273.5	TSL:1	c.670+6900A>G		intron	N/A	ENSP00000426255.1	Q9H3E2-1
	SNX25	ENST00000927314.1		c.1162+6900A>G		intron	N/A	ENSP00000597373.1

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

African (AFR) AF: 0.357 AC: 14783 AN: 41438

American (AMR) AF: 0.443 AC: 6764 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1543 AN: 3464

East Asian (EAS) AF: 0.527 AC: 2722 AN: 5168

South Asian (SAS) AF: 0.498 AC: 2400 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4169 AN: 10550

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30258 AN: 67940

Other (OTH) AF: 0.433 AC: 913 AN: 2108

Alfa AF: 0.439 Hom.: 53828

Bravo AF: 0.415

Asia WGS AF: 0.502 AC: 1741 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		0.60
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: rs1288547; hg19: chr4-186216136;