6-135636654-A-G

Variant names:

• chr6-135636654-A-G
• rs6902485
• ENST00000421378.4:n.199-5539A>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.199-5539A>G variant causes a intron change. The variant allele was found at a frequency of 0.179 in 169,752 control chromosomes in the GnomAD database, including 6,497 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 0.19 (6323 hom., cov: 32)
  • Exomes 𝑓: 0.094 (174 hom.)
• Consequence: AHI1-DT ENST00000421378.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• Publications: 2 publications found

Genes affected

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

HMGB1P17 (HGNC:39099): (high mobility group box 1 pseudogene 17)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421378.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1-DT	NR_026805.1		n.201-5539A>G		intron	N/A
	AHI1-DT	NR_152842.1		n.315-5539A>G		intron	N/A
	AHI1-DT	NR_152844.1		n.315-5539A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHI1-DT	ENST00000421378.4	TSL:1	n.199-5539A>G		intron	N/A
	HMGB1P17	ENST00000403495.2	TSL:6	n.60T>C		non_coding_transcript_exon	Exon 1 of 1
	AHI1-DT	ENST00000438618.2	TSL:3	n.439+803A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28646 AN: 152000 Hom.: 6310 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.0942 AC: 1662 AN: 17634 Hom.: 174 Cov.: 0 AF XY: 0.0906 AC XY: 977 AN XY: 10780

African (AFR) AF: 0.636 AC: 375 AN: 590

American (AMR) AF: 0.138 AC: 325 AN: 2350

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 44 AN: 324

East Asian (EAS) AF: 0.0643 AC: 68 AN: 1058

South Asian (SAS) AF: 0.121 AC: 229 AN: 1888

European-Finnish (FIN) AF: 0.0118 AC: 20 AN: 1692

Middle Eastern (MID) AF: 0.273 AC: 6 AN: 22

European-Non Finnish (NFE) AF: 0.0613 AC: 553 AN: 9018

Other (OTH) AF: 0.0607 AC: 42 AN: 692

GnomAD4 genome AF: 0.189 AC: 28713 AN: 152118 Hom.: 6323 Cov.: 32 AF XY: 0.182 AC XY: 13551 AN XY: 74356

African (AFR) AF: 0.538 AC: 22268 AN: 41424

American (AMR) AF: 0.130 AC: 1994 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.0492 AC: 255 AN: 5178

South Asian (SAS) AF: 0.0745 AC: 359 AN: 4816

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10610

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0434 AC: 2952 AN: 68022

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.0862 Hom.: 6154

Bravo AF: 0.214

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		4.3

Splicing

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

Other links and lift over

dbSNP: rs6902485; hg19: chr6-135957792;