rs564557542

Variant names:

• chr12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T
• rs564557542
• NM_018179.5:c.538_567delCCTTCTGGTGATGTGTCCCCTGGTGATGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_018179.5(ATF7IP):​c.538_567delCCTTCTGGTGATGTGTCCCCTGGTGATGCC​(p.Pro180_Ala189del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000588 in 1,613,580 control chromosomes in the GnomAD database, including 5 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (5 hom.)
• Consequence: ATF7IP NM_018179.5 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.51
• 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 -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018179.5.
• BP6: Variant 12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T is Benign according to our data. Variant chr12-14424441-TCTGGTGATGCCCCTTCTGGTGATGTGTCCC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3025287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.538_567delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro180_Ala189del	conservative_inframe_deletion	Exon 2 of 15	NP_060649.3
	ATF7IP	NM_181352.2		c.562_591delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro188_Ala197del	conservative_inframe_deletion	Exon 2 of 15	NP_851997.1	Q6VMQ6-4
	ATF7IP	NM_001388179.1		c.562_591delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro188_Ala197del	conservative_inframe_deletion	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.538_567delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro180_Ala189del	conservative_inframe_deletion	Exon 2 of 15	ENSP00000261168.4	Q6VMQ6-1
	ATF7IP	ENST00000544627.5	TSL:1	c.562_591delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro188_Ala197del	conservative_inframe_deletion	Exon 2 of 15	ENSP00000440440.1	Q6VMQ6-4
	ATF7IP	ENST00000540793.5	TSL:1	c.538_567delCCTTCTGGTGATGTGTCCCCTGGTGATGCC	p.Pro180_Ala189del	conservative_inframe_deletion	Exon 1 of 14	ENSP00000444589.1	Q6VMQ6-1

Frequencies

GnomAD3 genomes AF: 0.000691 AC: 105 AN: 151888 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000665 AC: 167 AN: 251282 AF XY: 0.000781

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00411

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000785

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000577 AC: 844 AN: 1461574 Hom.: 5 AF XY: 0.000666 AC XY: 484 AN XY: 727084

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.000291 AC: 13 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 218 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00226 AC: 195 AN: 86220

European-Finnish (FIN) AF: 0.000861 AC: 46 AN: 53420

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000249 AC: 277 AN: 1111822

Other (OTH) AF: 0.00118 AC: 71 AN: 60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000691 AC: 105 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.000754 AC XY: 56 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.000524 AC: 8 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67948

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00197 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=195/5	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs564557542; hg19: chr12-14577375;