7-101159505-A-G

Position:

• chr7-101159505-A-G

Variant summary

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

The ENST00000337619.11(AP1S1):​c.429+309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 343,222 control chromosomes in the GnomAD database, including 4,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1578 hom., cov: 31)
  • Exomes 𝑓: 0.17 (2847 hom.)
• Consequence: AP1S1 ENST00000337619.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0560

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]

MIR4653 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-101159505-A-G is Benign according to our data. Variant chr7-101159505-A-G is described in ClinVar as [Benign]. Clinvar id is 1291905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1S1	NM_001283.5	c.429+309A>G		intron_variant		ENST00000337619.11	NP_001274.1
MIR4653	NR_039797.1	n.33A>G		non_coding_transcript_exon_variant	1/1
MIR4653	unassigned_transcript_1291	n.-19A>G		upstream_gene_variant
MIR4653	unassigned_transcript_1290	n.*2A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1S1	ENST00000337619.11	c.429+309A>G		intron_variant		1	NM_001283.5	ENSP00000336666.5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20434 AN: 151912 Hom.: 1574 Cov.: 31

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.223 AC: 522 AN: 2346 Hom.: 46 AF XY: 0.227 AC XY: 299 AN XY: 1316

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.190

Gnomad SAS exome AF: 0.289

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.173 AC: 33021 AN: 191198 Hom.: 2847 Cov.: 0 AF XY: 0.177 AC XY: 17565 AN XY: 99058

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0974

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.134 AC: 20437 AN: 152024 Hom.: 1578 Cov.: 31 AF XY: 0.132 AC XY: 9841 AN XY: 74322

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.154

Alfa AF: 0.144 Hom.: 276

Bravo AF: 0.133

Asia WGS AF: 0.165 AC: 576 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	5.9
DANN	Benign	0.67

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: rs11983381; hg19: chr7-100802786;