rs587783178

Variant names:

• chr1-113895501-G-C
• rs17031980
• NM_001253852.3:c.1793-9C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-113895501-G-C
• chr1-113895501-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001253852.3(AP4B1):​c.1793-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,614,082 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (295 hom.)
• Consequence: AP4B1 NM_001253852.3 intron
• Scores: Splicing: ADA: 0.0003083
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.539
• Publications: 6 publications found

Genes affected

AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

AP4B1-AS1 (HGNC:44114): (AP4B1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-113895501-G-C is Benign according to our data. Variant chr1-113895501-G-C is described in ClinVar as Benign. ClinVar VariationId is 157719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253852.3. 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
	AP4B1	NM_001253852.3	MANE Select	c.1793-9C>G		intron	N/A	NP_001240781.1	Q9Y6B7-1
	AP4B1	NM_001438373.1		c.1793-9C>G		intron	N/A	NP_001425302.1
	AP4B1	NM_006594.5		c.1793-9C>G		intron	N/A	NP_006585.2	Q9Y6B7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4B1	ENST00000369569.6	TSL:1 MANE Select	c.1793-9C>G		intron	N/A	ENSP00000358582.1	Q9Y6B7-1
	AP4B1	ENST00000256658.8	TSL:1	c.1793-9C>G		intron	N/A	ENSP00000256658.4	Q9Y6B7-1
	AP4B1	ENST00000863127.1		c.1919-9C>G		intron	N/A	ENSP00000533186.1

Frequencies

GnomAD3 genomes AF: 0.00943 AC: 1435 AN: 152208 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0138

GnomAD2 exomes AF: 0.0191 AC: 4794 AN: 250914 AF XY: 0.0152

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.00884

Gnomad EAS exome AF: 0.0517

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000379

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.00506 AC: 7403 AN: 1461756 Hom.: 295 Cov.: 31 AF XY: 0.00457 AC XY: 3320 AN XY: 727180

African (AFR) AF: 0.000956 AC: 32 AN: 33472

American (AMR) AF: 0.0969 AC: 4334 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00926 AC: 242 AN: 26136

East Asian (EAS) AF: 0.0492 AC: 1951 AN: 39692

South Asian (SAS) AF: 0.00315 AC: 272 AN: 86238

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 0.000196 AC: 218 AN: 1111978

Other (OTH) AF: 0.00581 AC: 351 AN: 60390

GnomAD4 genome AF: 0.00940 AC: 1432 AN: 152326 Hom.: 35 Cov.: 32 AF XY: 0.0100 AC XY: 747 AN XY: 74494

African (AFR) AF: 0.00171 AC: 71 AN: 41570

American (AMR) AF: 0.0641 AC: 981 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5182

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68030

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.0164

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary spastic paraplegia 47 (2)
-	-	2	not specified (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.9
DANN	Benign	0.56
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.010		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: rs17031980; hg19: chr1-114438123; COSMIC: COSV56725554; COSMIC: COSV56725554;