rs12445135

Variant names:

• chr16-27374185-G-A
• rs12445135
• ENST00000722344.1:n.-74G>A

Variant summary

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

The ENST00000722344.1(ENSG00000294275):​n.-74G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 152,252 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.036 (216 hom., cov: 32)
• Consequence: ENSG00000294275 ENST00000722344.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 2 publications found

Genes affected

ENSG00000294275 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000294275	ENST00000722344.1	n.-74G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5465 AN: 152134 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.00816

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0359 AC: 5466 AN: 152252 Hom.: 216 Cov.: 32 AF XY: 0.0393 AC XY: 2925 AN XY: 74456

African (AFR) AF: 0.00813 AC: 338 AN: 41556

American (AMR) AF: 0.104 AC: 1594 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.0554 AC: 287 AN: 5180

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4820

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0310 AC: 2108 AN: 68010

Other (OTH) AF: 0.0378 AC: 80 AN: 2116

Alfa AF: 0.0327 Hom.: 160

Bravo AF: 0.0384

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		0.24

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12445135; hg19: chr16-27385506;