dbSNP rs12371762: ENSG00000257674:n.1639C>T (chr12-42288549-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000550858.1(ENSG00000257674):n.1639C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,602,254 control chromosomes in the GnomAD database, including 129,101 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 0.35 ( 9776 hom., cov: 32)

Exomes 𝑓: 0.40 ( 119325 hom. )

Consequence

ENSG00000257674
ENST00000550858.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47

Publications

5 publications found

Variant links:

Genes affected

ENSG00000257674 (HGNC:58593):

ENSG00000257674 links:

PPHLN1 (HGNC:19369): (periphilin 1) The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPHLN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP2P1		n.42288549C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257674	ENST00000550858.1 link	n.1639C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
PPHLN1	ENST00000549190.5 link	c.35-47334C>T		intron_variant	Intron 1 of 9	5		ENSP00000447168.1		F8W0Q9

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52703

AN:

151902

Hom.:

9773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.490

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.344

GnomAD4 exome

AF:

0.402

AC:

582567

AN:

1450234

Hom.:

119325

Cov.:

AF XY:

0.405

AC XY:

292555

AN XY:

721960

show subpopulations

African (AFR)

AF:

0.211

AC:

6993

AN:

33220

American (AMR)

AF:

0.275

AC:

12306

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

9298

AN:

26080

East Asian (EAS)

AF:

0.416

AC:

16496

AN:

39672

South Asian (SAS)

AF:

0.488

AC:

41922

AN:

85982

European-Finnish (FIN)

AF:

0.449

AC:

23981

AN:

53416

Middle Eastern (MID)

AF:

0.392

AC:

1622

AN:

4134

European-Non Finnish (NFE)

AF:

0.405

AC:

446463

AN:

1103094

Other (OTH)

AF:

0.392

AC:

23486

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16878

33756

50634

67512

84390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13810

27620

41430

55240

69050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.347

AC:

52726

AN:

152020

Hom.:

9776

Cov.:

AF XY:

0.354

AC XY:

26267

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.220

AC:

9134

AN:

41468

American (AMR)

AF:

0.308

AC:

4710

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1219

AN:

3470

East Asian (EAS)

AF:

0.418

AC:

2156

AN:

5154

South Asian (SAS)

AF:

0.481

AC:

2317

AN:

4818

European-Finnish (FIN)

AF:

0.458

AC:

4837

AN:

10560

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27071

AN:

67962

Other (OTH)

AF:

0.343

AC:

724

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1673

3346

5018

6691

8364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.365

Hom.:

3448

Bravo

AF:

0.324

Asia WGS

AF:

0.424

AC:

1470

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over