chr19-46838160-C-T

Position:

• chr19-46838160-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000601498.5(AP2S1):​c.*287G>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 0.0173 in 436,174 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (28 hom., cov: 32)
  • Exomes 𝑓: 0.019 (75 hom.)
• Consequence: AP2S1 ENST00000601498.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124

Genes affected

AP2S1 (HGNC:565): (adaptor related protein complex 2 subunit sigma 1) One of two major clathrin-associated adaptor complexes, AP-2, is a heterotetramer which is associated with the plasma membrane. This complex is composed of two large chains, a medium chain, and a small chain. This gene encodes the small chain of this complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-46838160-C-T is Benign according to our data. Variant chr19-46838160-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0149 (2270/152312) while in subpopulation NFE AF= 0.0239 (1625/68026). AF 95% confidence interval is 0.0229. There are 28 homozygotes in gnomad4. There are 1078 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2270 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP2S1	NM_004069.6			downstream_gene_variant		ENST00000263270.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2S1	ENST00000263270.11			downstream_gene_variant		1	NM_004069.6	P4

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2270 AN: 152194 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.00422

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0186 AC: 5285 AN: 283862 Hom.: 75 Cov.: 0 AF XY: 0.0190 AC XY: 2820 AN XY: 148576

Gnomad4 AFR exome AF: 0.00497

Gnomad4 AMR exome AF: 0.00822

Gnomad4 ASJ exome AF: 0.00345

Gnomad4 EAS exome AF: 0.0000532

Gnomad4 SAS exome AF: 0.0220

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.0228

Gnomad4 OTH exome AF: 0.0181

GnomAD4 genome AF: 0.0149 AC: 2270 AN: 152312 Hom.: 28 Cov.: 32 AF XY: 0.0145 AC XY: 1078 AN XY: 74480

Gnomad4 AFR AF: 0.00421

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0221

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0176 Hom.: 3

Bravo AF: 0.0136

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142218524; hg19: chr19-47341417;