6-146651937-G-A

Variant names:

• chr6-146651937-G-A
• rs9390411
• NM_024694.4:c.331-2198G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 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.331-2198G>A		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.331-2198G>A		intron	N/A	ENSP00000381036.3
	ADGB	ENST00000493950.6	TSL:1	n.331-2198G>A		intron	N/A	ENSP00000430244.1
	ADGB	ENST00000681847.1		c.331-2198G>A		intron	N/A	ENSP00000505524.1

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

African (AFR) AF: 0.736 AC: 30391 AN: 41294

American (AMR) AF: 0.675 AC: 10275 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2729 AN: 3462

East Asian (EAS) AF: 0.690 AC: 3542 AN: 5130

South Asian (SAS) AF: 0.832 AC: 3998 AN: 4808

European-Finnish (FIN) AF: 0.792 AC: 8302 AN: 10486

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.775 AC: 52560 AN: 67788

Other (OTH) AF: 0.726 AC: 1528 AN: 2104

Alfa AF: 0.764 Hom.: 198121

Bravo AF: 0.739

Asia WGS AF: 0.789 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.089
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: rs9390411; hg19: chr6-146973073;