7-101156292-A-G

Position:

• chr7-101156292-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001283.5(AP1S1):​c.4-302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 251,956 control chromosomes in the GnomAD database, including 27,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (15569 hom., cov: 32)
  • Exomes 𝑓: 0.46 (11935 hom.)
• Consequence: AP1S1 NM_001283.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0250

Genes affected

AP1S1 (HGNC:559): (adaptor related protein complex 1 subunit sigma 1) The protein encoded by this gene is part of the clathrin coat assembly complex which links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. This protein, as well as beta-prime-adaptin, gamma-adaptin, and the medium (mu) chain AP47, form the AP-1 assembly protein complex located at the Golgi vesicle. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-101156292-A-G is Benign according to our data. Variant chr7-101156292-A-G is described in ClinVar as [Benign]. Clinvar id is 1243303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1S1	NM_001283.5	c.4-302A>G		intron_variant		ENST00000337619.11	NP_001274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1S1	ENST00000337619.11	c.4-302A>G		intron_variant		1	NM_001283.5	ENSP00000336666.5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63098 AN: 151988 Hom.: 15571 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.461 AC: 46075 AN: 99850 Hom.: 11935 AF XY: 0.459 AC XY: 23378 AN XY: 50950

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.415 AC: 63096 AN: 152106 Hom.: 15569 Cov.: 32 AF XY: 0.418 AC XY: 31096 AN XY: 74346

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.408

Alfa AF: 0.507 Hom.: 20855

Bravo AF: 0.399

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.70

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: rs4727480; hg19: chr7-100799573;