12-14424047-A-G

Variant names:

• chr12-14424047-A-G
• rs371570170
• NM_018179.5:c.132A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018179.5(ATF7IP):​c.132A>G​(p.Leu44Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATF7IP NM_018179.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.706 with no splicing effect.

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.132A>G	p.Leu44Leu	synonymous	Exon 2 of 15	NP_060649.3
	ATF7IP	NM_181352.2		c.156A>G	p.Leu52Leu	synonymous	Exon 2 of 15	NP_851997.1	Q6VMQ6-4
	ATF7IP	NM_001388179.1		c.156A>G	p.Leu52Leu	synonymous	Exon 2 of 15	NP_001375108.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	ENST00000261168.9	TSL:5 MANE Select	c.132A>G	p.Leu44Leu	synonymous	Exon 2 of 15	ENSP00000261168.4	Q6VMQ6-1
	ATF7IP	ENST00000544627.5	TSL:1	c.156A>G	p.Leu52Leu	synonymous	Exon 2 of 15	ENSP00000440440.1	Q6VMQ6-4
	ATF7IP	ENST00000540793.5	TSL:1	c.132A>G	p.Leu44Leu	synonymous	Exon 1 of 14	ENSP00000444589.1	Q6VMQ6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.2
DANN	Benign	0.81
PhyloP100		0.71
PromoterAI		-0.0044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs371570170; hg19: chr12-14576981;