chr6-146651937-G-A

Position:

• chr6-146651937-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.331-2198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,486 control chromosomes in the GnomAD database, including 43,134 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 0.75 (43134 hom., cov: 31)
• Consequence: ADGB NM_024694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGB	NM_024694.4	c.331-2198G>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.331-2198G>A		intron_variant		5	NM_024694.4	ENSP00000381036	P4

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114079 AN: 151364 Hom.: 43098 Cov.: 31

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.644

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.754 AC: 114172 AN: 151486 Hom.: 43134 Cov.: 31 AF XY: 0.753 AC XY: 55714 AN XY: 74006

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.726

Alfa AF: 0.765 Hom.: 90279

Bravo AF: 0.739

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.63

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: rs9390411; hg19: chr6-146973073;