12-14469068-A-G

Variant names:

• chr12-14469068-A-G
• rs11055989
• NM_018179.5:c.2862+2478A>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.2862+2478A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,032 control chromosomes in the GnomAD database, including 6,104 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 0.26 (6104 hom., cov: 31)
• Consequence: ATF7IP NM_018179.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 5 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	NM_018179.5	MANE Select	c.2862+2478A>G		intron	N/A	NP_060649.3
	ATF7IP	NM_181352.2		c.2886+2478A>G		intron	N/A	NP_851997.1
	ATF7IP	NM_001388179.1		c.2883+2478A>G		intron	N/A	NP_001375108.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	ENST00000261168.9	TSL:5 MANE Select	c.2862+2478A>G		intron	N/A	ENSP00000261168.4
	ATF7IP	ENST00000544627.5	TSL:1	c.2886+2478A>G		intron	N/A	ENSP00000440440.1
	ATF7IP	ENST00000540793.5	TSL:1	c.2862+2478A>G		intron	N/A	ENSP00000444589.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39280 AN: 151914 Hom.: 6102 Cov.: 31

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.258 AC: 39285 AN: 152032 Hom.: 6104 Cov.: 31 AF XY: 0.262 AC XY: 19482 AN XY: 74294

African (AFR) AF: 0.0997 AC: 4140 AN: 41516

American (AMR) AF: 0.178 AC: 2714 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3468

East Asian (EAS) AF: 0.381 AC: 1972 AN: 5180

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4812

European-Finnish (FIN) AF: 0.459 AC: 4826 AN: 10514

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22487 AN: 67952

Other (OTH) AF: 0.258 AC: 545 AN: 2110

Alfa AF: 0.303 Hom.: 33230

Bravo AF: 0.232

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.3
DANN	Benign	0.89
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11055989; hg19: chr12-14622002;