1-113900413-C-G

Variant names:

• chr1-113900413-C-G
• rs3789613
• NM_001253852.3:c.618-13G>C

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.618-13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,610,424 control chromosomes in the GnomAD database, including 111,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9497 hom., cov: 32)
  • Exomes 𝑓: 0.36 (102173 hom.)
• Consequence: AP4B1 NM_001253852.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0520
• Publications: 16 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=-0.87).
• BP6: Variant 1-113900413-C-G is Benign according to our data. Variant chr1-113900413-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 157725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 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.618-13G>C		intron	N/A	NP_001240781.1	Q9Y6B7-1
	AP4B1	NM_001438373.1		c.618-13G>C		intron	N/A	NP_001425302.1
	AP4B1	NM_006594.5		c.618-13G>C		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.618-13G>C		intron	N/A	ENSP00000358582.1	Q9Y6B7-1
	AP4B1	ENST00000256658.8	TSL:1	c.618-13G>C		intron	N/A	ENSP00000256658.4	Q9Y6B7-1
	AP4B1	ENST00000863127.1		c.618-13G>C		intron	N/A	ENSP00000533186.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48911 AN: 151986 Hom.: 9503 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.386 AC: 94825 AN: 245408 AF XY: 0.376

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.773

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.364 AC: 530324 AN: 1458320 Hom.: 102173 Cov.: 39 AF XY: 0.360 AC XY: 261163 AN XY: 725402

African (AFR) AF: 0.117 AC: 3897 AN: 33404

American (AMR) AF: 0.514 AC: 22435 AN: 43680

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 7173 AN: 25988

East Asian (EAS) AF: 0.739 AC: 29295 AN: 39668

South Asian (SAS) AF: 0.252 AC: 21605 AN: 85688

European-Finnish (FIN) AF: 0.431 AC: 22913 AN: 53204

Middle Eastern (MID) AF: 0.293 AC: 1675 AN: 5712

European-Non Finnish (NFE) AF: 0.360 AC: 399928 AN: 1110722

Other (OTH) AF: 0.355 AC: 21403 AN: 60254

GnomAD4 genome AF: 0.322 AC: 48916 AN: 152104 Hom.: 9497 Cov.: 32 AF XY: 0.329 AC XY: 24494 AN XY: 74346

African (AFR) AF: 0.129 AC: 5366 AN: 41494

American (AMR) AF: 0.461 AC: 7043 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3472

East Asian (EAS) AF: 0.764 AC: 3959 AN: 5180

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4672 AN: 10560

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.360 AC: 24502 AN: 67980

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.324 Hom.: 1589

Bravo AF: 0.323

Asia WGS AF: 0.487 AC: 1692 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hereditary spastic paraplegia 47 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		0.052
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: rs3789613; hg19: chr1-114443035; COSMIC: COSV56724001; COSMIC: COSV56724001;