NM_001283.5:c.4-302A>G

Variant names:

• chr7-101156292-A-G
• rs4727480
• NM_001283.5:c.4-302A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

AP1S1 Gene-Disease associations (from GenCC):

• MEDNIK syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Orphanet, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S1	NM_001283.5	MANE Select	c.4-302A>G		intron	N/A	NP_001274.1	P61966-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S1	ENST00000337619.11	TSL:1 MANE Select	c.4-302A>G		intron	N/A	ENSP00000336666.5	P61966-1
	AP1S1	ENST00000429457.1	TSL:5	c.127-302A>G		intron	N/A	ENSP00000399902.1	H7C1E4
	AP1S1	ENST00000926144.1		c.4-302A>G		intron	N/A	ENSP00000596203.1

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

African (AFR) AF: 0.162 AC: 654 AN: 4040

American (AMR) AF: 0.522 AC: 2318 AN: 4440

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2108 AN: 3548

East Asian (EAS) AF: 0.106 AC: 796 AN: 7478

South Asian (SAS) AF: 0.285 AC: 1909 AN: 6688

European-Finnish (FIN) AF: 0.575 AC: 2664 AN: 4630

Middle Eastern (MID) AF: 0.492 AC: 249 AN: 506

European-Non Finnish (NFE) AF: 0.522 AC: 32419 AN: 62138

Other (OTH) AF: 0.463 AC: 2958 AN: 6382

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

African (AFR) AF: 0.172 AC: 7158 AN: 41512

American (AMR) AF: 0.512 AC: 7821 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3466

East Asian (EAS) AF: 0.147 AC: 760 AN: 5184

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4824

European-Finnish (FIN) AF: 0.615 AC: 6496 AN: 10558

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35933 AN: 67980

Other (OTH) AF: 0.408 AC: 861 AN: 2110

Alfa AF: 0.489 Hom.: 28769

Bravo AF: 0.399

Asia WGS AF: 0.231 AC: 807 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4727480; hg19: chr7-100799573;