Genetic Variant RIPOR1:c.-245A>G (chr16-67518392-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000621378.4(CTCF-DT):n.469-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,480 control chromosomes in the GnomAD database, including 75,536 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 1.0 ( 75469 hom., cov: 33)

Exomes 𝑓: 1.0 ( 67 hom. )

Consequence

CTCF-DT
ENST00000621378.4 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.718

Publications

1 publications found

Variant links:

Genes affected

RIPOR1 (HGNC:25836): (RHO family interacting cell polarization regulator 1) Enables 14-3-3 protein binding activity. Involved in several processes, including establishment of Golgi localization; negative regulation of Rho guanyl-nucleotide exchange factor activity; and negative regulation of Rho protein signal transduction. Located in Golgi apparatus; cell leading edge; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

RIPOR1 links:

CTCF-DT (HGNC:55409): (CTCF divergent transcript)

CTCF-DT links:

LOC100505942 (HGNC:):

LOC100505942 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000621378.4. 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
	LOC100505942	NR_104656.1		n.430-7T>C		splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CTCF-DT	ENST00000613438.4	TSL:3	n.171-7T>C	splice_region intron	N/A
CTCF-DT	ENST00000621378.4	TSL:2	n.469-7T>C	splice_region intron	N/A
CTCF-DT	ENST00000748474.1		n.184-7T>C	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.995

AC:

151471

AN:

152228

Hom.:

75406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

0.996

Gnomad EAS

AF:

0.875

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.996

GnomAD4 exome

AF:

1.00

AC:

134

AN:

134

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Age Distribution

Exome Hom

Variant carriers

<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:

0.995

AC:

151593

AN:

152346

Hom.:

75469

Cov.:

AF XY:

0.994

AC XY:

74070

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.999

AC:

41542

AN:

41588

American (AMR)

AF:

1.00

AC:

15295

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.996

AC:

3459

AN:

3472

East Asian (EAS)

AF:

0.876

AC:

4538

AN:

5182

South Asian (SAS)

AF:

0.995

AC:

4804

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10626

AN:

10626

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

68020

AN:

68030

Other (OTH)

AF:

0.996

AC:

2104

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.999

Hom.:

50371

Bravo

AF:

0.994

Asia WGS

AF:

0.958

AC:

3333

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.2

(source)

DANN

Benign

0.71

PhyloP100

0.72

PromoterAI

0.0053

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over