6-146669909-A-G

Variant names:

• chr6-146669909-A-G
• rs2226067
• NM_024694.4:c.840-2311A>G

Variant summary

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

The NM_024694.4(ADGB):​c.840-2311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,018 control chromosomes in the GnomAD database, including 48,812 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 0.80 (48812 hom., cov: 31)
• Consequence: ADGB NM_024694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 3 publications found

Genes affected

ADGB (HGNC:21212): (androglobin) Predicted to enable calcium-dependent cysteine-type endopeptidase activity; heme binding activity; and oxygen binding activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024694.4. 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
	ADGB	NM_024694.4	MANE Select	c.840-2311A>G		intron	N/A	NP_078970.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGB	ENST00000397944.8	TSL:5 MANE Select	c.840-2311A>G		intron	N/A	ENSP00000381036.3
	ADGB	ENST00000493950.6	TSL:1	n.613-2311A>G		intron	N/A	ENSP00000430244.1
	ADGB	ENST00000681847.1		c.840-2311A>G		intron	N/A	ENSP00000505524.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121421 AN: 151900 Hom.: 48755 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.800 AC: 121539 AN: 152018 Hom.: 48812 Cov.: 31 AF XY: 0.801 AC XY: 59500 AN XY: 74260

African (AFR) AF: 0.868 AC: 36003 AN: 41496

American (AMR) AF: 0.836 AC: 12739 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3472

East Asian (EAS) AF: 0.701 AC: 3597 AN: 5128

South Asian (SAS) AF: 0.860 AC: 4148 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8049 AN: 10568

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51943 AN: 67982

Other (OTH) AF: 0.768 AC: 1617 AN: 2106

Alfa AF: 0.773 Hom.: 196452

Bravo AF: 0.802

Asia WGS AF: 0.822 AC: 2857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.67
DANN	Benign	0.61
PhyloP100		-0.54
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: rs2226067; hg19: chr6-146991045;