chr1-113894348-T-C

Variant names:

• chr1-113894348-T-C
• rs10745340
• NM_001253852.3:c.*717A>G

Variant summary

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

The NM_001253852.3(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 NM_001253852.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 19 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4B1	NM_001253852.3	MANE Select	c.*717A>G		3_prime_UTR	Exon 10 of 10	NP_001240781.1
	AP4B1	NM_001438373.1		c.*717A>G		3_prime_UTR	Exon 11 of 11	NP_001425302.1
	AP4B1	NM_006594.5		c.*717A>G		3_prime_UTR	Exon 11 of 11	NP_006585.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP4B1	ENST00000369569.6	TSL:1 MANE Select	c.*717A>G		3_prime_UTR	Exon 10 of 10	ENSP00000358582.1
	AP4B1	ENST00000460653.2	TSL:3	n.*2007A>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000518881.1
	AP4B1	ENST00000713588.1		n.*2048A>G		non_coding_transcript_exon	Exon 11 of 11	ENSP00000518880.1

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

African (AFR) AF: 0.129 AC: 5371 AN: 41540

American (AMR) AF: 0.461 AC: 7036 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3468

East Asian (EAS) AF: 0.776 AC: 4018 AN: 5176

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4826

European-Finnish (FIN) AF: 0.442 AC: 4671 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24488 AN: 67986

Other (OTH) AF: 0.343 AC: 724 AN: 2112

Alfa AF: 0.346 Hom.: 40855

Bravo AF: 0.323

Asia WGS AF: 0.490 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.61
PhyloP100		0.045

Splicing

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

Other links and lift over

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