rs9403813

chr6-146749369-A-Gchr6-146749369-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105378040 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGB	NM_024694.4	c.3366-3161A>G		intron_variant		ENST00000397944.8
LOC105378040	XR_943093.2	n.60-12345T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGB	ENST00000397944.8	c.3366-3161A>G		intron_variant		5	NM_024694.4	P4

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

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.182

Alfa AF: 0.171 Hom.: 524

Bravo AF: 0.175

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.71

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: rs9403813; hg19: chr6-147070505; COSMIC: COSV62228442;