rs12666075

Variant names:

• chr7-151023221-G-T
• rs12666075
• NM_001317056.2:c.660-15C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151023221-G-T
• chr7-151023221-G-A
• chr7-151023221-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317056.2(ATG9B):​c.660-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,480 control chromosomes in the GnomAD database, including 32,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.20 (3550 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29215 hom.)
• Consequence: ATG9B NM_001317056.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633
• Publications: 9 publications found

Genes affected

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317056.2. 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
	ATG9B	NM_001317056.2	MANE Select	c.660-15C>A		intron	N/A	NP_001303985.1	Q674R7-1
	ATG9B	NR_073169.1		n.343-15C>A		intron	N/A
	ATG9B	NR_133652.1		n.736-15C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.660-15C>A		intron	N/A	ENSP00000491504.1	Q674R7-1
	ATG9B	ENST00000605952.5	TSL:1	n.660-15C>A		intron	N/A	ENSP00000475737.2	Q674R7-1
	ATG9B	ENST00000617967.4	TSL:1	n.309-15C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30308 AN: 151736 Hom.: 3533 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.237 AC: 58901 AN: 249024 AF XY: 0.220

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.416

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.186 AC: 271430 AN: 1461630 Hom.: 29215 Cov.: 36 AF XY: 0.182 AC XY: 132452 AN XY: 727112

African (AFR) AF: 0.184 AC: 6171 AN: 33474

American (AMR) AF: 0.490 AC: 21934 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3795 AN: 26130

East Asian (EAS) AF: 0.435 AC: 17285 AN: 39698

South Asian (SAS) AF: 0.138 AC: 11858 AN: 86222

European-Finnish (FIN) AF: 0.208 AC: 11111 AN: 53356

Middle Eastern (MID) AF: 0.167 AC: 961 AN: 5768

European-Non Finnish (NFE) AF: 0.168 AC: 187014 AN: 1111876

Other (OTH) AF: 0.187 AC: 11301 AN: 60384

GnomAD4 genome AF: 0.200 AC: 30343 AN: 151850 Hom.: 3550 Cov.: 32 AF XY: 0.204 AC XY: 15155 AN XY: 74266

African (AFR) AF: 0.183 AC: 7524 AN: 41188

American (AMR) AF: 0.349 AC: 5335 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2231 AN: 5166

South Asian (SAS) AF: 0.130 AC: 629 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 2174 AN: 10602

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.167 AC: 11352 AN: 68004

Other (OTH) AF: 0.201 AC: 425 AN: 2110

Alfa AF: 0.170 Hom.: 1456

Bravo AF: 0.217

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12666075; hg19: chr7-150720308; COSMIC: COSV65059918; COSMIC: COSV65059918;