chr12-14475135-A-G

Variant names:

• chr12-14475135-A-G
• rs4346018
• NM_018179.5:c.2863-755A>G

Variant summary

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

The NM_018179.5(ATF7IP):​c.2863-755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,086 control chromosomes in the GnomAD database, including 9,342 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 0.33 (9342 hom., cov: 32)
• Consequence: ATF7IP NM_018179.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 4 publications found

Genes affected

ATF7IP (HGNC:20092): (activating transcription factor 7 interacting protein) ATF7IP is a multifunctional nuclear protein that associates with heterochromatin. It can act as a transcriptional coactivator or corepressor depending upon its binding partners (summary by Liu et al., 2009 [PubMed 19106100]).[supplied by OMIM, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018179.5. 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
	ATF7IP	NM_018179.5	MANE Select	c.2863-755A>G		intron	N/A	NP_060649.3
	ATF7IP	NM_181352.2		c.2887-755A>G		intron	N/A	NP_851997.1	Q6VMQ6-4
	ATF7IP	NM_001388179.1		c.2884-755A>G		intron	N/A	NP_001375108.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	ENST00000261168.9	TSL:5 MANE Select	c.2863-755A>G		intron	N/A	ENSP00000261168.4	Q6VMQ6-1
	ATF7IP	ENST00000544627.5	TSL:1	c.2887-755A>G		intron	N/A	ENSP00000440440.1	Q6VMQ6-4
	ATF7IP	ENST00000540793.5	TSL:1	c.2863-755A>G		intron	N/A	ENSP00000444589.1	Q6VMQ6-1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49776 AN: 151968 Hom.: 9331 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.328 AC: 49813 AN: 152086 Hom.: 9342 Cov.: 32 AF XY: 0.327 AC XY: 24312 AN XY: 74334

African (AFR) AF: 0.136 AC: 5655 AN: 41508

American (AMR) AF: 0.466 AC: 7116 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1772 AN: 5178

South Asian (SAS) AF: 0.427 AC: 2060 AN: 4826

European-Finnish (FIN) AF: 0.315 AC: 3329 AN: 10554

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27490 AN: 67976

Other (OTH) AF: 0.359 AC: 756 AN: 2108

Alfa AF: 0.376 Hom.: 5946

Bravo AF: 0.336

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.52
PhyloP100		-0.26
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: rs4346018; hg19: chr12-14628069;