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
• 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]

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 VariationId 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.

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.429+309A>G		intron	N/A	NP_001274.1	P61966-1
	MIR4653	NR_039797.1		n.33A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S1	ENST00000337619.11	TSL:1 MANE Select	c.429+309A>G		intron	N/A	ENSP00000336666.5	P61966-1
	AP1S1	ENST00000429457.1	TSL:5	c.552+309A>G		intron	N/A	ENSP00000399902.1	H7C1E4
	AP1S1	ENST00000926144.1		c.456+309A>G		intron	N/A	ENSP00000596203.1

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

African (AFR) AF: 0.0772 AC: 333 AN: 4316

American (AMR) AF: 0.132 AC: 525 AN: 3986

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 1158 AN: 6266

East Asian (EAS) AF: 0.0974 AC: 869 AN: 8926

South Asian (SAS) AF: 0.223 AC: 4624 AN: 20756

European-Finnish (FIN) AF: 0.116 AC: 1451 AN: 12460

Middle Eastern (MID) AF: 0.167 AC: 244 AN: 1458

European-Non Finnish (NFE) AF: 0.181 AC: 21872 AN: 120968

Other (OTH) 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

African (AFR) AF: 0.0717 AC: 2973 AN: 41476

American (AMR) AF: 0.129 AC: 1967 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.106 AC: 548 AN: 5184

South Asian (SAS) AF: 0.185 AC: 885 AN: 4794

European-Finnish (FIN) AF: 0.0938 AC: 990 AN: 10556

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11849 AN: 67952

Other (OTH) AF: 0.154 AC: 325 AN: 2108

Alfa AF: 0.141 Hom.: 278

Bravo AF: 0.133

Asia WGS AF: 0.165 AC: 576 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		0.056
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: rs11983381; hg19: chr7-100802786;