dbSNP rs4996522: RAPGEF6:c.*1489C>T (chr5-131425777-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016340.6(RAPGEF6):c.*1489C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,900 control chromosomes in the GnomAD database, including 4,328 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 0.23 ( 4324 hom., cov: 31)

Exomes 𝑓: 0.28 ( 4 hom. )

Consequence

RAPGEF6
NM_016340.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.433

Publications

8 publications found

Variant links:

Genes affected

RAPGEF6 (HGNC:20655): (Rap guanine nucleotide exchange factor 6) Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

RAPGEF6 links:

ENSG00000273217 (HGNC:):

ENSG00000273217 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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RAPGEF6	NM_016340.6 link	c.*1489C>T	3_prime_UTR_variant	Exon 28 of 28	ENST00000509018.6	NP_057424.3
RAPGEF6	NM_001164386.2 link	c.*1489C>T	3_prime_UTR_variant	Exon 29 of 29		NP_001157858.1
RAPGEF6	NM_001164387.2 link	c.*1489C>T	3_prime_UTR_variant	Exon 29 of 29		NP_001157859.1
RAPGEF6	NM_001164388.2 link	c.*1489C>T	3_prime_UTR_variant	Exon 28 of 28		NP_001157860.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
RAPGEF6	ENST00000509018.6 link	c.*1489C>T	3_prime_UTR_variant	Exon 28 of 28	1	NM_016340.6	ENSP00000421684.1
RAPGEF6	ENST00000671916.1 link	c.*1489C>T	3_prime_UTR_variant	Exon 18 of 18			ENSP00000500379.1
ENSG00000273217	ENST00000514667.1 link	c.*1489C>T	downstream_gene_variant		2		ENSP00000426948.1
RAPGEF6	ENST00000512611.5 link	n.*110C>T	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

34996

AN:

151642

Hom.:

4313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.285

AC:

AN:

144

Hom.:

Cov.:

AF XY:

0.317

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.290

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.231

AC:

35041

AN:

151756

Hom.:

4324

Cov.:

AF XY:

0.239

AC XY:

17739

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.191

AC:

7913

AN:

41356

American (AMR)

AF:

0.251

AC:

3829

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1031

AN:

3468

East Asian (EAS)

AF:

0.486

AC:

2497

AN:

5136

South Asian (SAS)

AF:

0.254

AC:

1222

AN:

4820

European-Finnish (FIN)

AF:

0.369

AC:

3859

AN:

10462

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13891

AN:

67958

Other (OTH)

AF:

0.214

AC:

452

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1285

2570

3856

5141

6426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.210

Hom.:

4561

Bravo

AF:

0.222

Asia WGS

AF:

0.368

AC:

1282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.4

(source)

DANN

Benign

0.58

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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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