Genetic Variant NM_001278293.3:c.186-18T>C (chr3-97780597-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001278293.3(ARL6):c.186-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,604,612 control chromosomes in the GnomAD database, including 577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 207 hom., cov: 32)

Exomes 𝑓: 0.017 ( 370 hom. )

Consequence

ARL6
NM_001278293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0630

Variant links:

Genes affected

ARL6 (HGNC:13210): (ADP ribosylation factor like GTPase 6) The protein encoded by this gene belongs to the ARF-like (ADP ribosylation factor-like) sub-family of the ARF family of GTP-binding proteins which are involved in regulation of intracellular traffic. Mutations in this gene are associated with Bardet-Biedl syndrome (BBS). A vision-specific transcript, encoding long isoform BBS3L, has been described (PMID: 20333246). [provided by RefSeq, Apr 2016]

ARL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-97780597-T-C is Benign according to our data. Variant chr3-97780597-T-C is described in ClinVar as [Benign]. Clinvar id is 262014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-97780597-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL6	NM_001278293.3 link	c.186-18T>C		intron_variant	Intron 3 of 7	ENST00000463745.6	NP_001265222.1	Q9H0F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL6	ENST00000463745.6 link	c.186-18T>C		intron_variant	Intron 3 of 7	2	NM_001278293.3	ENSP00000419619.1		Q9H0F7-1

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5867

AN:

152122

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0951

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0358

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0218

AC:

5473

AN:

251108

Hom.:

116

AF XY:

0.0202

AC XY:

2737

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.0999

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0452

Gnomad EAS exome

AF:

0.0396

Gnomad SAS exome

AF:

0.0124

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0172

AC:

25035

AN:

1452372

Hom.:

370

Cov.:

AF XY:

0.0171

AC XY:

12374

AN XY:

723358

show subpopulations

Gnomad4 AFR exome

AF:

0.0970

Gnomad4 AMR exome

AF:

0.0174

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.0290

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00260

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0231

GnomAD4 genome

AF:

0.0385

AC:

5866

AN:

152240

Hom.:

207

Cov.:

AF XY:

0.0380

AC XY:

2832

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0948

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.0359

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0274

Hom.:

Bravo

AF:

0.0438

Asia WGS

AF:

0.0280

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 3;C3150808:Retinitis pigmentosa 55

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.45

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over