7-121133900-A-G

Variant names:

• chr7-121133900-A-G
• rs61128227
• NM_024913.5:c.1648+7A>G

Variant summary

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

The NM_024913.5(CPED1):​c.1648+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,495,960 control chromosomes in the GnomAD database, including 127,620 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (11004 hom., cov: 32)
  • Exomes 𝑓: 0.41 (116616 hom.)
• Consequence: CPED1 NM_024913.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001293
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 12 publications found

Genes affected

CPED1 (HGNC:26159): (cadherin like and PC-esterase domain containing 1) Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024913.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	NM_024913.5	MANE Select	c.1648+7A>G		splice_region intron	N/A	NP_079189.4
	CPED1	NM_001105533.1		c.1648+7A>G		splice_region intron	N/A	NP_001099003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPED1	ENST00000310396.10	TSL:1 MANE Select	c.1648+7A>G		splice_region intron	N/A	ENSP00000309772.5
	CPED1	ENST00000450913.6	TSL:1	c.1648+7A>G		splice_region intron	N/A	ENSP00000406122.2
	CPED1	ENST00000423795.5	TSL:1	c.988+7A>G		splice_region intron	N/A	ENSP00000415573.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51496 AN: 151858 Hom.: 11001 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.379

GnomAD2 exomes AF: 0.436 AC: 100947 AN: 231516 AF XY: 0.434

Gnomad AFR exome AF: 0.0757

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.632

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.408 AC: 548735 AN: 1343984 Hom.: 116616 Cov.: 20 AF XY: 0.409 AC XY: 275469 AN XY: 673508

African (AFR) AF: 0.0706 AC: 2130 AN: 30164

American (AMR) AF: 0.630 AC: 25933 AN: 41164

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 8718 AN: 24838

East Asian (EAS) AF: 0.646 AC: 24694 AN: 38238

South Asian (SAS) AF: 0.410 AC: 32554 AN: 79350

European-Finnish (FIN) AF: 0.402 AC: 21294 AN: 52984

Middle Eastern (MID) AF: 0.445 AC: 2411 AN: 5412

European-Non Finnish (NFE) AF: 0.402 AC: 408126 AN: 1015656

Other (OTH) AF: 0.407 AC: 22875 AN: 56178

GnomAD4 genome AF: 0.339 AC: 51498 AN: 151976 Hom.: 11004 Cov.: 32 AF XY: 0.345 AC XY: 25657 AN XY: 74278

African (AFR) AF: 0.0838 AC: 3482 AN: 41530

American (AMR) AF: 0.558 AC: 8496 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3187 AN: 5152

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4822

European-Finnish (FIN) AF: 0.390 AC: 4120 AN: 10574

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27679 AN: 67906

Other (OTH) AF: 0.375 AC: 789 AN: 2102

Alfa AF: 0.381 Hom.: 5523

Bravo AF: 0.341

Asia WGS AF: 0.439 AC: 1522 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs61128227; hg19: chr7-120773954; COSMIC: COSV59998976; COSMIC: COSV59998976;