chr19-46838237-G-A

Position:

• chr19-46838237-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004069.6(AP2S1):​c.*210C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 590,196 control chromosomes in the GnomAD database, including 9,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2596 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6960 hom.)
• Consequence: AP2S1 NM_004069.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-46838237-G-A is Benign according to our data. Variant chr19-46838237-G-A is described in ClinVar as [Benign]. Clinvar id is 1277070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2S1	NM_004069.6	c.*210C>T		3_prime_UTR_variant	5/5	ENST00000263270.11	NP_004060.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2S1	ENST00000263270.11	c.*210C>T		3_prime_UTR_variant	5/5	1	NM_004069.6	ENSP00000263270	P4

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27126 AN: 152092 Hom.: 2596 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.169 AC: 74006 AN: 437986 Hom.: 6960 Cov.: 3 AF XY: 0.165 AC XY: 37993 AN XY: 230630

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0297

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.178 AC: 27129 AN: 152210 Hom.: 2596 Cov.: 32 AF XY: 0.173 AC XY: 12855 AN XY: 74436

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.181

Alfa AF: 0.191 Hom.: 410

Bravo AF: 0.183

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.84
CADD	Benign	0.22
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs17653; hg19: chr19-47341494;