6-135689660-A-G

Variant names:

• chr6-135689660-A-G
• rs2273069
• ENST00000421378.4:n.456A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000421378.4(AHI1-DT):​n.456A>G 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 0.247 in 151,890 control chromosomes in the GnomAD database, including 5,497 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 0.25 (5492 hom., cov: 32)
  • Exomes 𝑓: 0.40 (5 hom.)
• Consequence: AHI1-DT ENST00000421378.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 3 publications found

Genes affected

AHI1-DT (HGNC:32526): (AHI1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHI1-DT	NR_026805.1	n.458A>G		non_coding_transcript_exon_variant	Exon 4 of 4
AHI1-DT	NR_152842.1	n.572A>G		non_coding_transcript_exon_variant	Exon 5 of 6
AHI1-DT	NR_152844.1	n.572A>G		non_coding_transcript_exon_variant	Exon 5 of 5
AHI1-DT	NR_152845.1	n.696A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHI1-DT	ENST00000421378.4	n.456A>G		non_coding_transcript_exon_variant	Exon 4 of 4	1
AHI1-DT	ENST00000579944.1	n.154A>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
AHI1-DT	ENST00000653664.1	n.596A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37412 AN: 151704 Hom.: 5484 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.397 AC: 27 AN: 68 Hom.: 5 Cov.: 0 AF XY: 0.364 AC XY: 16 AN XY: 44

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.444 AC: 24 AN: 54

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.246 AC: 37419 AN: 151822 Hom.: 5492 Cov.: 32 AF XY: 0.244 AC XY: 18092 AN XY: 74174

African (AFR) AF: 0.0832 AC: 3443 AN: 41386

American (AMR) AF: 0.314 AC: 4783 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2074 AN: 5152

South Asian (SAS) AF: 0.362 AC: 1740 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2008 AN: 10540

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21397 AN: 67908

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.153 Hom.: 295

Bravo AF: 0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.59
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2273069; hg19: chr6-136010798;