8-22748605-A-G

Variant names:

• chr8-22748605-A-G
• rs2313168
• NM_144962.3:c.358-21385T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144962.3(PEBP4):​c.358-21385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 150,582 control chromosomes in the GnomAD database, including 60,906 homozygotes. 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: 𝑓 0.90 (60906 hom., cov: 25)
• Consequence: PEBP4 NM_144962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• Publications: 3 publications found

Genes affected

PEBP4 (HGNC:28319): (phosphatidylethanolamine binding protein 4) The phosphatidylethanolamine (PE)-binding proteins, including PEBP4, are an evolutionarily conserved family of proteins with pivotal biologic functions, such as lipid binding and inhibition of serine proteases (Wang et al., 2004 [PubMed 15302887]).[supplied by OMIM, Dec 2008]

LOC124901908 (HGNC:):

EGR3-AS1 (HGNC:58186):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144962.3. 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
	PEBP4	NM_144962.3	MANE Select	c.358-21385T>C		intron	N/A	NP_659399.2	Q96S96
	PEBP4	NM_001363233.2		c.358-21385T>C		intron	N/A	NP_001350162.1	Q96S96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	ENST00000256404.8	TSL:1 MANE Select	c.358-21385T>C		intron	N/A	ENSP00000256404.6	Q96S96
	PEBP4	ENST00000901323.1		c.358-21385T>C		intron	N/A	ENSP00000571382.1
	PEBP4	ENST00000901324.1		c.358-21385T>C		intron	N/A	ENSP00000571383.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 134710 AN: 150466 Hom.: 60855 Cov.: 25

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.908

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.895 AC: 134817 AN: 150582 Hom.: 60906 Cov.: 25 AF XY: 0.897 AC XY: 65941 AN XY: 73496

African (AFR) AF: 0.757 AC: 30811 AN: 40712

American (AMR) AF: 0.945 AC: 14301 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3312 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5036 AN: 5040

South Asian (SAS) AF: 0.958 AC: 4565 AN: 4766

European-Finnish (FIN) AF: 0.957 AC: 9975 AN: 10424

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63781 AN: 67766

Other (OTH) AF: 0.910 AC: 1887 AN: 2074

Alfa AF: 0.935 Hom.: 23143

Bravo AF: 0.888

Asia WGS AF: 0.971 AC: 3374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.076
DANN	Benign	0.57
PhyloP100		-0.99
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2313168;

hg19: chr8-22606118;