chr6-146652317-G-A

Position:

• chr6-146652317-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024694.4(ADGB):​c.331-1818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,118 control chromosomes in the GnomAD database, including 49,938 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 0.81 (49938 hom., cov: 32)
• Consequence: ADGB NM_024694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGB	NM_024694.4	c.331-1818G>A		intron_variant		ENST00000397944.8	NP_078970.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGB	ENST00000397944.8	c.331-1818G>A		intron_variant		5	NM_024694.4	ENSP00000381036	P4

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122785 AN: 152000 Hom.: 49890 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.808 AC: 122898 AN: 152118 Hom.: 49938 Cov.: 32 AF XY: 0.807 AC XY: 59975 AN XY: 74348

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.780

Alfa AF: 0.774 Hom.: 60249

Bravo AF: 0.813

Asia WGS AF: 0.803 AC: 2790 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.39

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: rs9322069; hg19: chr6-146973453;