rs6928455

Variant names:

• chr6-135496997-C-T
• rs6928455
• NM_001134831.2:c.-140+191G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-135496997-C-T
• chr6-135496997-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001134831.2(AHI1):​c.-140+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,264 control chromosomes in the GnomAD database, including 55,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (55907 hom., cov: 32)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.927
• Publications: 1 publications found

Genes affected

AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

AHI1 Gene-Disease associations (from GenCC):

• Joubert syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, ClinGen, Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 6-135496997-C-T is Benign according to our data. Variant chr6-135496997-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134831.2. 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
	AHI1	NM_001134831.2	MANE Select	c.-140+191G>A		intron	N/A	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.-55+586G>A		intron	N/A	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.-311+586G>A		intron	N/A	NP_001337432.1	Q8N157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1	ENST00000265602.11	TSL:1 MANE Select	c.-140+191G>A		intron	N/A	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.-55+586G>A		intron	N/A	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.-55+191G>A		intron	N/A	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128554 AN: 152146 Hom.: 55895 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.852

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.845 AC: 128613 AN: 152264 Hom.: 55907 Cov.: 32 AF XY: 0.850 AC XY: 63308 AN XY: 74452

African (AFR) AF: 0.611 AC: 25336 AN: 41500

American (AMR) AF: 0.894 AC: 13675 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3319 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4963 AN: 5182

South Asian (SAS) AF: 0.948 AC: 4579 AN: 4828

European-Finnish (FIN) AF: 0.976 AC: 10376 AN: 10626

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63421 AN: 68040

Other (OTH) AF: 0.852 AC: 1801 AN: 2114

Alfa AF: 0.853 Hom.: 8081

Bravo AF: 0.829

Asia WGS AF: 0.903 AC: 3137 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.90
PhyloP100		-0.93
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6928455; hg19: chr6-135818135;