rs71725890

Variant names:

• chr6-135358205-TGTGA-T
• rs71725890
• NM_001134831.2:c.3110-22_3110-19delTCAC

Your query was ambiguous. Multiple possible variants found:

• chr6-135358205-TGTGA-T
• chr6-135358205-TGTGA-TGTGAGTGA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001134831.2(AHI1):​c.3110-22_3110-19delTCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 1,607,222 control chromosomes in the GnomAD database, including 837 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (443 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (394 hom.)
• Consequence: AHI1 NM_001134831.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.16
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 6-135358205-TGTGA-T is Benign according to our data. Variant chr6-135358205-TGTGA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 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.3110-22_3110-19delTCAC		intron	N/A	NP_001128303.1	Q8N157-1
	AHI1	NM_001134830.2		c.3110-22_3110-19delTCAC		intron	N/A	NP_001128302.1	Q8N157-1
	AHI1	NM_001350503.2		c.3110-22_3110-19delTCAC		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.3110-22_3110-19delTCAC		intron	N/A	ENSP00000265602.6	Q8N157-1
	AHI1	ENST00000367800.8	TSL:1	c.3110-22_3110-19delTCAC		intron	N/A	ENSP00000356774.4	Q8N157-1
	AHI1	ENST00000457866.6	TSL:1	c.3110-22_3110-19delTCAC		intron	N/A	ENSP00000388650.2	Q8N157-1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6535 AN: 152144 Hom.: 441 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0111 AC: 2734 AN: 247056 AF XY: 0.00856

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.000400

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00118

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.00477 AC: 6940 AN: 1454960 Hom.: 394 AF XY: 0.00418 AC XY: 3025 AN XY: 724080

African (AFR) AF: 0.144 AC: 4785 AN: 33144

American (AMR) AF: 0.0121 AC: 539 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.000514 AC: 44 AN: 85616

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53362

Middle Eastern (MID) AF: 0.0130 AC: 75 AN: 5754

European-Non Finnish (NFE) AF: 0.000677 AC: 749 AN: 1106954

Other (OTH) AF: 0.0122 AC: 734 AN: 60126

GnomAD4 genome AF: 0.0431 AC: 6557 AN: 152262 Hom.: 443 Cov.: 32 AF XY: 0.0423 AC XY: 3151 AN XY: 74458

African (AFR) AF: 0.145 AC: 6039 AN: 41528

American (AMR) AF: 0.0246 AC: 376 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000867 AC: 59 AN: 68012

Other (OTH) AF: 0.0355 AC: 75 AN: 2112

Alfa AF: 0.0197 Hom.: 38

Bravo AF: 0.0498

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
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: rs71725890; hg19: chr6-135679343;