chr7-44114226-G-A

Position:

• chr7-44114226-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001129.5(AEBP1):​c.3442G>A​(p.Val1148Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0305 in 1,611,706 control chromosomes in the GnomAD database, including 912 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.021 (57 hom., cov: 33)
  • Exomes 𝑓: 0.031 (855 hom.)
• Consequence: AEBP1 NM_001129.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.83

Genes affected

AEBP1 (HGNC:303): (AE binding protein 1) This gene encodes a member of carboxypeptidase A protein family. The encoded protein may function as a transcriptional repressor and play a role in adipogenesis and smooth muscle cell differentiation. Studies in mice suggest that this gene functions in wound healing and abdominal wall development. Overexpression of this gene is associated with glioblastoma. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053476095).
• BP6: Variant 7-44114226-G-A is Benign according to our data. Variant chr7-44114226-G-A is described in ClinVar as [Benign]. Clinvar id is 1226463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3184/150028) while in subpopulation NFE AF= 0.0355 (2387/67236). AF 95% confidence interval is 0.0343. There are 57 homozygotes in gnomad4. There are 1497 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AEBP1	NM_001129.5	c.3442G>A	p.Val1148Ile	missense_variant	21/21	ENST00000223357.8
AEBP1	XM_011515162.2	c.3364G>A	p.Val1122Ile	missense_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AEBP1	ENST00000223357.8	c.3442G>A	p.Val1148Ile	missense_variant	21/21	1	NM_001129.5	P1
AEBP1	ENST00000450684.2	c.2167G>A	p.Val723Ile	missense_variant	8/8	2
AEBP1	ENST00000413907.1	c.*1639G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	2

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3182 AN: 149910 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.00614

Gnomad AMI AF: 0.00773

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00762

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0228

GnomAD3 exomes AF: 0.0205 AC: 5142 AN: 251340 Hom.: 72 AF XY: 0.0210 AC XY: 2851 AN XY: 135874

Gnomad AFR exome AF: 0.00609

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0155

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00924

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.0328

Gnomad OTH exome AF: 0.0222

GnomAD4 exome AF: 0.0315 AC: 46034 AN: 1461678 Hom.: 855 Cov.: 34 AF XY: 0.0309 AC XY: 22498 AN XY: 727156

Gnomad4 AFR exome AF: 0.00463

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00951

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0253

GnomAD4 genome AF: 0.0212 AC: 3184 AN: 150028 Hom.: 57 Cov.: 33 AF XY: 0.0204 AC XY: 1497 AN XY: 73320

Gnomad4 AFR AF: 0.00612

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0148

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00805

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0355

Gnomad4 OTH AF: 0.0226

Alfa AF: 0.0294 Hom.: 165

Bravo AF: 0.0203

TwinsUK AF: 0.0431 AC: 160

ALSPAC AF: 0.0436 AC: 168

ESP6500AA AF: 0.00953 AC: 42

ESP6500EA AF: 0.0372 AC: 320

ExAC AF: 0.0210 AC: 2546

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0293

EpiControl AF: 0.0318

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.0053	T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.97	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.096	T;T
Polyphen		0.0020	B;B
Vest4		0.25
MPC		0.30
ClinPred		0.0067	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs13898; hg19: chr7-44153825;