7-101159505-A-G

Variant names:

• chr7-101159505-A-G
• rs11983381
• NM_001283.5:c.429+309A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001283.5(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 NM_001283.5 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:41562): (microRNA 4653) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AP1S1	NM_001283.5	c.429+309A>G		intron_variant	Intron 4 of 4	ENST00000337619.11	NP_001274.1
MIR4653	NR_039797.1	n.33A>G		non_coding_transcript_exon_variant	Exon 1 of 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 rank	TSL	MANE	Protein	Appris	UniProt
AP1S1	ENST00000337619.11	c.429+309A>G		intron_variant	Intron 4 of 4	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

GnomAD2 exomes AF: 0.223 AC: 522 AN: 2346 AF XY: 0.227

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 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 AC: 333 AN: 4316

Gnomad4 AMR exome AF: 0.132 AC: 525 AN: 3986

Gnomad4 ASJ exome AF: 0.185 AC: 1158 AN: 6266

Gnomad4 EAS exome AF: 0.0974 AC: 869 AN: 8926

Gnomad4 SAS exome AF: 0.223 AC: 4624 AN: 20756

Gnomad4 FIN exome AF: 0.116 AC: 1451 AN: 12460

Gnomad4 NFE exome AF: 0.181 AC: 21872 AN: 120968

Gnomad4 Remaining exome AF: 0.161 AC: 1945 AN: 12062

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 AC: 0.07168 AN: 0.07168

Gnomad4 AMR AF: 0.129 AC: 0.128714 AN: 0.128714

Gnomad4 ASJ AF: 0.171 AC: 0.171083 AN: 0.171083

Gnomad4 EAS AF: 0.106 AC: 0.10571 AN: 0.10571

Gnomad4 SAS AF: 0.185 AC: 0.184606 AN: 0.184606

Gnomad4 FIN AF: 0.0938 AC: 0.0937855 AN: 0.0937855

Gnomad4 NFE AF: 0.174 AC: 0.174373 AN: 0.174373

Gnomad4 OTH AF: 0.154 AC: 0.154175 AN: 0.154175

Alfa AF: 0.141 Hom.: 278

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.67
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

Publications

LitVar

Other links and lift over

dbSNP: rs11983381; hg19: chr7-100802786;