NM_001129.5:c.3442G>A

Variant names:

• chr7-44114226-G-A
• rs13898
• NM_001129.5:c.3442G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 13 publications found

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]

AEBP1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, classic-like, 2

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129.5. 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
	AEBP1	NM_001129.5	MANE Select	c.3442G>A	p.Val1148Ile	missense	Exon 21 of 21	NP_001120.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AEBP1	ENST00000223357.8	TSL:1 MANE Select	c.3442G>A	p.Val1148Ile	missense	Exon 21 of 21	ENSP00000223357.3	Q8IUX7-1
	AEBP1	ENST00000910440.1		c.3454G>A	p.Val1152Ile	missense	Exon 21 of 21	ENSP00000580499.1
	AEBP1	ENST00000910438.1		c.3436G>A	p.Val1146Ile	missense	Exon 21 of 21	ENSP00000580497.1

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

GnomAD2 exomes AF: 0.0205 AC: 5142 AN: 251340 AF XY: 0.0210

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 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

African (AFR) AF: 0.00463 AC: 155 AN: 33480

American (AMR) AF: 0.0126 AC: 564 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 421 AN: 26136

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

South Asian (SAS) AF: 0.00951 AC: 820 AN: 86248

European-Finnish (FIN) AF: 0.0165 AC: 878 AN: 53358

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.0374 AC: 41636 AN: 1111892

Other (OTH) AF: 0.0253 AC: 1525 AN: 60394

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

African (AFR) AF: 0.00612 AC: 249 AN: 40666

American (AMR) AF: 0.0154 AC: 232 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 51 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5048

South Asian (SAS) AF: 0.00805 AC: 38 AN: 4722

European-Finnish (FIN) AF: 0.0161 AC: 170 AN: 10532

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0355 AC: 2387 AN: 67236

Other (OTH) AF: 0.0226 AC: 47 AN: 2082

Alfa AF: 0.0289 Hom.: 306

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

ClinVar submissions

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	0.11
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
MetaRNN	Benign	0.0053	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.22
Sift	Uncertain	0.014	D
Sift4G	Benign	0.096	T
Polyphen		0.0020	B
Vest4		0.25
MPC		0.30
ClinPred		0.0067	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.48
Mutation Taster		=97/3	polymorphism (auto)

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: rs13898; hg19: chr7-44153825;