1-113894348-T-C

Position:

• chr1-113894348-T-C

Variant summary

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

The ENST00000369569.6(AP4B1):​c.*717A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,148 control chromosomes in the GnomAD database, including 9,540 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 0.32 (9540 hom., cov: 33)
• Consequence: AP4B1 ENST00000369569.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP4B1	NM_001253852.3	c.*717A>G		3_prime_UTR_variant	10/10	ENST00000369569.6	NP_001240781.1
AP4B1-AS1	NR_125965.1	n.415-3520T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP4B1	ENST00000369569.6	c.*717A>G		3_prime_UTR_variant	10/10	1	NM_001253852.3	ENSP00000358582	P1
AP4B1-AS1	ENST00000419536.1	n.247-3520T>C		intron_variant, non_coding_transcript_variant		2
AP4B1	ENST00000460653.2	c.*2007A>G		3_prime_UTR_variant, NMD_transcript_variant	11/11	3		ENSP00000518881
AP4B1	ENST00000713588.1	c.*2048A>G		3_prime_UTR_variant, NMD_transcript_variant	11/11			ENSP00000518880

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48966 AN: 152030 Hom.: 9547 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.322 AC: 48970 AN: 152148 Hom.: 9540 Cov.: 33 AF XY: 0.330 AC XY: 24507 AN XY: 74358

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.343

Alfa AF: 0.348 Hom.: 19323

Bravo AF: 0.323

Asia WGS AF: 0.490 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10745340; hg19: chr1-114436970; COSMIC: COSV56723986;