Genetic Variant ENSG00000274895:n.777C>G (chr1-213985643-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000610409.1(ENSG00000274895):n.777C>G 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 0.426 in 152,192 control chromosomes in the GnomAD database, including 14,611 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 0.43 ( 14610 hom., cov: 34)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

ENSG00000274895
ENST00000610409.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Publications

11 publications found

Variant links:

COSMIC-nc: COSV65293272

Genes affected

ENSG00000274895 (HGNC:):

ENSG00000274895 links:

PROX1 (HGNC:9459): (prospero homeobox 1) The protein encoded by this gene is a member of the homeobox transcription factor family. Members of this family contain a homeobox domain that consists of a 60-amino acid helix-turn-helix structure that binds DNA and RNA. The protein encoded by this gene is conserved across vertebrates and may play an essential role during development. Altered levels of this protein have been reported in cancers of different organs, such as colon, brain, blood, breast, pancreas, liver and esophagus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

PROX1 links:

PROX1-AS1 (HGNC:43656): (PROX1 antisense RNA 1)

PROX1-AS1 links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PROX1-AS1	NR_037850.2 link	n.85+426C>G		intron_variant	Intron 1 of 5
PROX1	XM_011509773.3 link	c.-68+2320G>C		intron_variant	Intron 1 of 4		XP_011508075.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000274895	ENST00000610409.1 link	n.777C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
PROX1	ENST00000471129.1 link	c.-68+2320G>C	intron_variant	Intron 1 of 1	3	ENSP00000419517.1	C9JU29
PROX1-AS1	ENST00000433082.6 link	n.62+2678C>G	intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64804

AN:

152068

Hom.:

14612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.595

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.477

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.498

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.426

AC:

64815

AN:

152186

Hom.:

14610

Cov.:

AF XY:

0.422

AC XY:

31412

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.269

AC:

11191

AN:

41546

American (AMR)

AF:

0.463

AC:

7088

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

1656

AN:

3470

East Asian (EAS)

AF:

0.529

AC:

2733

AN:

5162

South Asian (SAS)

AF:

0.557

AC:

2684

AN:

4822

European-Finnish (FIN)

AF:

0.381

AC:

4035

AN:

10590

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.498

AC:

33849

AN:

67988

Other (OTH)

AF:

0.431

AC:

907

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1883

3765

5648

7530

9413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.447

Hom.:

1959

Bravo

AF:

0.423

Asia WGS

AF:

0.520

AC:

1808

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.7

(source)

DANN

Benign

0.73

PhyloP100

0.058

Splicing

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

Publications

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1-213985643-G-C

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