rs17791685

Variant names:

• chr3-57272583-C-A
• rs17791685
• NM_012096.3:c.*2896C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-57272583-C-A
• chr3-57272583-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012096.3(APPL1):​c.*2896C>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 0.183 in 151,862 control chromosomes in the GnomAD database, including 2,840 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 0.18 (2840 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: APPL1 NM_012096.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 11 publications found

Genes affected

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

ASB14 (HGNC:19766): (ankyrin repeat and SOCS box containing 14) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2008]

LOC105377102 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012096.3. 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
	APPL1	NM_012096.3	MANE Select	c.*2896C>A		3_prime_UTR	Exon 22 of 22	NP_036228.1	Q9UKG1
	ASB14	NM_001142733.3	MANE Select	c.*23-2965G>T		intron	N/A	NP_001136205.2	A6NK59-3
	ASB14	NM_130387.5		c.*23-2965G>T		intron	N/A	NP_569058.1	A6NK59-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APPL1	ENST00000288266.8	TSL:1 MANE Select	c.*2896C>A		3_prime_UTR	Exon 22 of 22	ENSP00000288266.3	Q9UKG1
	ASB14	ENST00000487349.6	TSL:1 MANE Select	c.*23-2965G>T		intron	N/A	ENSP00000419199.1	A6NK59-3
	APPL1	ENST00000855522.1		c.*2896C>A		3_prime_UTR	Exon 21 of 21	ENSP00000525581.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27707 AN: 151702 Hom.: 2832 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.167 AC: 7 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.147 AC XY: 5 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 7 AN: 42

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.183 AC: 27745 AN: 151820 Hom.: 2840 Cov.: 31 AF XY: 0.178 AC XY: 13228 AN XY: 74180

African (AFR) AF: 0.249 AC: 10286 AN: 41322

American (AMR) AF: 0.152 AC: 2322 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5176

South Asian (SAS) AF: 0.111 AC: 535 AN: 4806

European-Finnish (FIN) AF: 0.179 AC: 1886 AN: 10536

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12113 AN: 67932

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.176 Hom.: 3208

Bravo AF: 0.185

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		-0.15
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: rs17791685; hg19: chr3-57306611;