chr6-146749369-A-G

Variant names:

• chr6-146749369-A-G
• rs9403813
• NM_024694.4:c.3366-3161A>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.3366-3161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,110 control chromosomes in the GnomAD database, including 2,526 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 0.17 (2526 hom., cov: 32)
• Consequence: ADGB NM_024694.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 0 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]

ENSG00000306991 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 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.3366-3161A>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.3366-3161A>G		intron	N/A	ENSP00000381036.3
	ADGB	ENST00000493950.6	TSL:1	n.*4197-3161A>G		intron	N/A	ENSP00000430244.1
	ADGB	ENST00000681847.1		c.3366-3161A>G		intron	N/A	ENSP00000505524.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26540 AN: 151992 Hom.: 2522 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.175 AC: 26561 AN: 152110 Hom.: 2526 Cov.: 32 AF XY: 0.172 AC XY: 12781 AN XY: 74340

African (AFR) AF: 0.176 AC: 7285 AN: 41490

American (AMR) AF: 0.125 AC: 1907 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2002 AN: 5146

South Asian (SAS) AF: 0.228 AC: 1103 AN: 4830

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10596

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11905 AN: 67992

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.171 Hom.: 540

Bravo AF: 0.175

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		0.18
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: rs9403813; hg19: chr6-147070505; COSMIC: COSV62228442;