dbSNP rs14375: KBTBD11-OT1:n.*5190G>T (chr8-1958464-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000635855.1(KBTBD11-OT1):n.*5190G>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 0.935 in 152,252 control chromosomes in the GnomAD database, including 66,559 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 0.93 ( 66556 hom., cov: 32)

Exomes 𝑓: 0.88 ( 3 hom. )

Consequence

KBTBD11-OT1
ENST00000635855.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

11 publications found

Variant links:

Genes affected

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ARHGEF10 Gene-Disease associations (from GenCC):

autosomal dominant slowed nerve conduction velocity
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
hereditary peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ARHGEF10 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.*1201G>T		3_prime_UTR_variant	Exon 29 of 29	ENST00000349830.8	NP_055444.2	O15013-5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KBTBD11-OT1	ENST00000635855.1 link	n.*5190G>T	non_coding_transcript_exon_variant	Exon 30 of 30	5		ENSP00000489726.1	A0A1B0GTJ5
ARHGEF10	ENST00000349830.8 link	c.*1201G>T	3_prime_UTR_variant	Exon 29 of 29	1	NM_014629.4	ENSP00000340297.3	O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.*5190G>T	3_prime_UTR_variant	Exon 30 of 30	5		ENSP00000489726.1	A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.935

AC:

142198

AN:

152126

Hom.:

66496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.916

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.930

Gnomad ASJ

AF:

0.927

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.985

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.934

Gnomad OTH

AF:

0.919

GnomAD4 exome

AF:

0.875

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

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:

1.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.935

AC:

142317

AN:

152244

Hom.:

66556

Cov.:

AF XY:

0.938

AC XY:

69831

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.916

AC:

38044

AN:

41518

American (AMR)

AF:

0.930

AC:

14231

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.927

AC:

3220

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5174

AN:

5184

South Asian (SAS)

AF:

0.985

AC:

4752

AN:

4826

European-Finnish (FIN)

AF:

0.968

AC:

10267

AN:

10610

Middle Eastern (MID)

AF:

0.898

AC:

264

AN:

294

European-Non Finnish (NFE)

AF:

0.934

AC:

63519

AN:

68022

Other (OTH)

AF:

0.920

AC:

1942

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

474

949

1423

1898

2372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.932

Hom.:

124825

Bravo

AF:

0.930

Asia WGS

AF:

0.985

AC:

3426

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.1

(source)

DANN

Benign

0.51

PhyloP100

0.016

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