12-14434367-A-G

Variant names:

• chr12-14434367-A-G
• rs3213764
• NM_018179.5:c.1589A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018179.5(ATF7IP):​c.1589A>G​(p.Lys530Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,571,092 control chromosomes in the GnomAD database, including 170,778 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14742 hom., cov: 33)
  • Exomes 𝑓: 0.46 (156036 hom.)
• Consequence: ATF7IP NM_018179.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.11
• Publications: 62 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3941526E-4).
• BP6: Variant 12-14434367-A-G is Benign according to our data. Variant chr12-14434367-A-G is described in ClinVar as Benign. ClinVar VariationId is 1271269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 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.1589A>G	p.Lys530Arg	missense	Exon 3 of 15	NP_060649.3
	ATF7IP	NM_181352.2		c.1613A>G	p.Lys538Arg	missense	Exon 3 of 15	NP_851997.1
	ATF7IP	NM_001388179.1		c.1610A>G	p.Lys537Arg	missense	Exon 3 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.1589A>G	p.Lys530Arg	missense	Exon 3 of 15	ENSP00000261168.4
	ATF7IP	ENST00000544627.5	TSL:1	c.1613A>G	p.Lys538Arg	missense	Exon 3 of 15	ENSP00000440440.1
	ATF7IP	ENST00000540793.5	TSL:1	c.1589A>G	p.Lys530Arg	missense	Exon 2 of 14	ENSP00000444589.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64993 AN: 151964 Hom.: 14741 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.465 AC: 113212 AN: 243266 AF XY: 0.471

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.586

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.463 AC: 657043 AN: 1419010 Hom.: 156036 Cov.: 28 AF XY: 0.465 AC XY: 328899 AN XY: 707682

African (AFR) AF: 0.258 AC: 8425 AN: 32622

American (AMR) AF: 0.377 AC: 16214 AN: 43040

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13376 AN: 25726

East Asian (EAS) AF: 0.618 AC: 23950 AN: 38742

South Asian (SAS) AF: 0.444 AC: 37190 AN: 83722

European-Finnish (FIN) AF: 0.593 AC: 31616 AN: 53288

Middle Eastern (MID) AF: 0.454 AC: 2565 AN: 5646

European-Non Finnish (NFE) AF: 0.461 AC: 496812 AN: 1077294

Other (OTH) AF: 0.456 AC: 26895 AN: 58930

GnomAD4 genome AF: 0.427 AC: 65003 AN: 152082 Hom.: 14742 Cov.: 33 AF XY: 0.434 AC XY: 32229 AN XY: 74342

African (AFR) AF: 0.280 AC: 11622 AN: 41506

American (AMR) AF: 0.378 AC: 5768 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3095 AN: 5178

South Asian (SAS) AF: 0.446 AC: 2152 AN: 4828

European-Finnish (FIN) AF: 0.606 AC: 6387 AN: 10540

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.481 AC: 32666 AN: 67974

Other (OTH) AF: 0.436 AC: 920 AN: 2112

Alfa AF: 0.464 Hom.: 75294

Bravo AF: 0.402

TwinsUK AF: 0.458 AC: 1697

ALSPAC AF: 0.470 AC: 1813

ESP6500AA AF: 0.297 AC: 1310

ESP6500EA AF: 0.487 AC: 4184

ExAC AF: 0.471 AC: 57130

Asia WGS AF: 0.461 AC: 1601 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.00014	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.049
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.056	T
Polyphen		0.97	D
Vest4		0.057
MPC		0.31
ClinPred		0.014	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.024
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.020		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: rs3213764; hg19: chr12-14587301; COSMIC: COSV53766209;