rs2226067

chr6-146669909-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4	c.840-2311A>G		intron_variant		ENST00000397944.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8	c.840-2311A>G		intron_variant		5	NM_024694.4	P4
ADGB	ENST00000493950.6	c.613-2311A>G		intron_variant, NMD_transcript_variant		1
ADGB	ENST00000681847.1	c.840-2311A>G		intron_variant				A2
ADGB	ENST00000326929.8	n.881-2311A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.768

Alfa AF: 0.768 Hom.: 92383

Bravo AF: 0.802

Asia WGS AF: 0.822 AC: 2857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.67
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2226067; hg19: chr6-146991045;